GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels float64 0 2	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
P62837	Q9C026	1	binding	up-regulates activity	0.425	Collectively, these results indicated that TRIM9 is an E3 ligase for its self-ubiquitination and that the ubiquitination of TRIM9 likely serves as a signal for proteasomal degradation. As shown in Fig. 1A, TRIM9 was ubiquitinated by itself when incubated with UbcH5b. In contrast, ubiquitination was observed when incubated with other E2 enzymes. These results suggest that TRIM9 cooperates with UbcH5b for its self-ubiquitination. N	SIGNOR-271420
P53350	P78527	2	phosphorylation	up-regulates activity	0.425	Moreover, PLK1 phosphorylates DNA-PKcs directly on Ser 3205 invitro, suggesting that DNA-PKcs Ser 3205 is a direct target of PLK1 in mitosis.	SIGNOR-278188
Q9Y2G2	P55211	1	binding	down-regulates	0.425	Tucan is a recently identified card-containing protein that can complex with caspase-9 and prevent cytochrome c-induced caspase activation.	SIGNOR-146663
P00441	P21796	1	binding	down-regulates activity	0.425	Misfolded Mutant SOD1 Directly Inhibits VDAC1 Conductance in a Mouse Model of Inherited ALS\|With conformation-specific antibodies, we now demonstrate that misfolded mutant SOD1 binds directly to the voltage-dependent anion channel (VDAC1), an integral membrane protein imbedded in the outer mitochondrial membrane.	SIGNOR-262798
O15194	P84022	1	dephosphorylation	up-regulates activity	0.424	Dephosphorylation of Smad2/3 Linkers by SCP2 and SCP3\|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity	SIGNOR-248306
P36888	O75874	1	phosphorylation	up-regulates activity	0.424	Moreover, in an in vitro kinase assay, purified recombinant FLT3 (rFLT3) phosphorylated recombinant IDH2 R140Q mutant but did not alter its catalytic activity (Figure 1C), whereas rFLT3 phosphorylated mIDH1 protein and enhanced its catalytic activity	SIGNOR-267630
Q96PY6	P21796	1	phosphorylation	down-regulates	0.424	Nek1 phosphorylates vdac1 on ser193. Wild-type vdac1 assumes an open configuration, but closes and prevents cytochrome c efflux when phosphorylated by nek1. A vdac1-ser193ala mutant, which cannot be phosphorylated by nek1 under identical conditions, remains open and constitutively allows cytochrome c efflux.	SIGNOR-164222
Q16236	Q9UPY5	1	transcriptional regulation	up-regulates quantity by expression	0.424	NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification. NFE2L2 directly binds to the promoter region of SLC7A11, leading to increased expression of this transporter, which in turn contributes to the resistance to ferroptosis and to radiotherapy	SIGNOR-279867
Q00987	Q9Y6B2	1	polyubiquitination	down-regulates quantity by destabilization	0.424	Degradation of EID-1 occurs via ubiquitin-dependent proteolysis and correlates with MDM2 binding. These results are consistent with a model wherein destruction of EID-1 is linked to its ability to interact with MDM2 via either p300 or pRB.	SIGNOR-272582
P23443	P36956	1	phosphorylation	up-regulates activity	0.424	Besides promoting protein synthesis, S6K1 also phosphorylates and activates sterol regulatory element binding protein 1 and 2 (SREBP and SREBP2), which promotes de novo lipid synthesis that is critical for cell growth and proliferation.\|Besides promoting protein synthesis, S6K1 also phosphorylates and activates sterol regulatory element-binding protein 1 and 2 (SREBP and SREBP2), which promotes de novo lipid synthesis that is critical for cell growth and proliferation ( xref ).	SIGNOR-280120
P68400	Q9UNN4	1	phosphorylation	up-regulates activity	0.424	ALF was able to stabilize the binding of TBP to DNA, but it could not stabilize TBP mutants A184E, N189E, E191R, and R205E nor could it facilitate binding of the TBP-like factor TRF2/TLF to a consensus TATA element. However, phosphorylation of ALF with casein kinase II resulted in the partial restoration of complex formation using mutant TBPs. \| Because the residues involved (Ser-280, Ser-281, Ser-316, and Ser-321) are conserved in ALF (Ser-356, Ser-357, Ser-418, and Ser-423), we tested whether its activity might also be affected by this modification. We first showed that ALF and TFIIAα/β polypeptides incubated with casein kinase II and [γ-32P]ATP could be labeled.	SIGNOR-250873
P53350	Q13526	1	phosphorylation	up-regulates	0.424	Here we demonstrate that ser-65 in pin1 is the major site for plk1-specific phosphorylation, and the polo-box domain of plk1 is required for this phosphorylation. Interestingly, the phosphorylation of pin1 by plk1 does not affect its isomerase activity but rather is linked to its protein stability. pin1 is ubiquitinated in hela s3 cells, and substitution of glu for ser-65 reduces the ubiquitination of pin1.	SIGNOR-139919
P00519	Q9BX66	1	phosphorylation	up-regulates activity	0.424	We have here identified Tyr360 in CAP as a major phosphorylation site by c-Abl, although Tyr 632 also might contribute since its substitution in combination with the Y360F mutation reduced the phosphorylation of CAP to a very low level. Y360 in CAP is the major phosphorylation site of c-Abl. Since Tyr326 was not a major c-Abl phosphorylation site, we sought to identify a putative other kinase that might be involved in the phosphorylation of Y326 in CAP.	SIGNOR-278153
Q9HBW1	P78352	1	binding	up-regulates activity	0.424	A possible function for the NGL–PSD-95 interaction is to couple trans-synaptic adhesion events to the recruitment of PSD-95 and other PSD-95-associated postsynaptic proteins. PSD-95 and liprin-α may be key synaptic scaffolding proteins that couple trans-synaptic adhesions to the assembly of synaptic proteins/vesicles	SIGNOR-264051
O14595	P84022	1	dephosphorylation	up-regulates activity	0.424	Dephosphorylation of Smad2/3 Linkers by SCP2 and SCP3\|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity	SIGNOR-248293
Q05655	O15162	1	phosphorylation	up-regulates	0.424	Following the induction of apoptosis, however, phosphorylation of serine residues decreased and it increased on threonine, consistent with the predicted pkc phosphorylation site at thr-161. Transfection of cho cells with scramblase and pkc_, but not scramblase or pkc_ alone, increased scramblase activity	SIGNOR-76904
Q08345	P30408	1	binding	up-regulates activity	0.424	Gao et al have demonstrated that in metastatic breast cancer cell, DDR1 interacts with cell surface Transmembrane 4 L Six Family Member 1 (TM4SF1) and regulates tumor dormancy and reactivation [3]. The interaction between DDR1 and TM4SF1 is collagen dependent and control Protein Kinase C Alpha (PKCa) mediated downstream JAK-STAT signaling pathway [3] (Figure 3). Interestingly the data also showed that TM4SF1 failed to interact with DDR2.	SIGNOR-272400
Q8TEV9	O75385	1	binding	down-regulates activity	0.424	While focusing on the role of SMCR8 during autophagy initiation, we found that kinase activity and gene expression of ULK1 are increased upon SMCR8 depletion.	SIGNOR-252029
P08581	Q03135	1	phosphorylation	up-regulates activity	0.424	Findings obtained using SNU-449 cells suggested that c-Met positively regulated CAV1 activity.\|Inhibition of c-Met activation abolished phosphorylation of CAV1 on Tyrosine 14.	SIGNOR-279080
P49841	P60484	1	phosphorylation	down-regulates activity	0.424	Gsk3beta Phosphorylates pten at thr-366 in intact cells phosphorylation of pten at thr-366 reduces the activity of pten in cells	SIGNOR-236641
P02452	Q16832	1	binding	up-regulates activity	0.424	The Discoidin Domain Receptors (DDRs) constitute a unique set of receptor tyrosine kinases that signal in response to collagen.\|Consistent with this view128, we showed that ectopic expression of DDR1b or DDR2 in HT1080 cells elicited a potent growth inhibitory effect only when the cells were cultured on 2D or 3D COL1 matrices, in agreement with previous studies in melanoma48, breast cancer76,78, and lung cancer cells74,75.	SIGNOR-272342
P29376	P29353	1	phosphorylation	up-regulates	0.424	Recently, we demonstrated that ltk utilizes shc and irs-1 as two major substrates and while both equally activate the ras pathway, only irs-1 suppresses apoptosis of hematopoietic cells.	SIGNOR-49625
Q9H2X6	Q92793	1	phosphorylation	up-regulates activity	0.424	Moreover, we show that HIPK2 strongly potentiates the transcriptional activity of CREB-binding protein.\|We show that HIPK2 interacts with and phosphorylates several regions of CBP.	SIGNOR-279191
P25116	P09471	1	binding	up-regulates activity	0.424	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257011
Q14192	Q9NYA1	1	binding	down-regulates activity	0.424	FHL2/SLIM3 decreases cardiomyocyte survival by inhibitory interaction with sphingosine kinase-1.	SIGNOR-237775
Q9GZV5	P43699	1	binding	up-regulates	0.424	Taz also binds to the transcription factor ttf-1 that is involved in formation and differentiation of the lungs and respiratory epithelia, and stimulates the production of pulmonary surfactant.	SIGNOR-143472
P31749	O75376	1	phosphorylation	down-regulates	0.424	Akt-induced phosphorylation of n-cor at serine 1450 contributes to its misfolded conformational dependent loss (mcdl) in acute myeloid leukemia of the m5 subtype.	SIGNOR-198913
P00519	P37840	1	phosphorylation	up-regulates quantity	0.424	C-Abl interacts with alpha-synuclein and phosphorylates alpha-synuclein at Y39 (XREF_FIG) .	SIGNOR-279582
P00519	Q14247	1	phosphorylation	up-regulates activity	0.424	Because phosphorylation by c-Abl augments nmMLCK-cortactin interaction to a greater degree than does pp60src phosphorylation, it is likely that phosphorylation sites on nmMLCK unique to c-Abl (i.e., other than Y464 and Y846) are responsible for this enhanced protein-protein interaction.\|Moreover, our data indicate that cortactin is itself rapidly phosphorylated on Y486 by c-Abl in EC after S1P (Figure 9).	SIGNOR-278504
Q7KZI7	P46939	1	phosphorylation	up-regulates	0.424	Par-1b, interacts with the utrophin-dg complex, and positively regulates the interaction between utrophin and dg. Ser1258 within r9 is specifically phosphorylated by par-1b.	SIGNOR-161915
P31749	P54578	1	phosphorylation	up-regulates activity	0.424	Phosphorylation and activation of ubiquitin-specific protease-14 by Akt regulates the ubiquitin-proteasome system\|These results suggested S432 as a major and S143 as a minor phosphorylation site of Akt.	SIGNOR-265056
Q70Z35	P60953	1	guanine nucleotide exchange factor	up-regulates activity	0.423	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260572
Q00534	P05412	1	phosphorylation	up-regulates quantity	0.423	CDK6 additionally induced c-Jun phosphorylation, but did not activate JNK, as determined by examining JNK phosphorylation at various time-points.\|CDK6 upregulates c-Jun expression.	SIGNOR-280222
Q9Y243	Q9UKV8	1	phosphorylation	up-regulates	0.423	Phosphorylation of argonaute 2 at serine-387 facilitates its localization to processing bodies, akt3-mediated phosphorylation of ago2 is a molecular switch between target mrna cleavage and translational repression activities of ago2	SIGNOR-178416
P45983	Q6SZW1	1	phosphorylation	down-regulates activity	0.423	C-Jun N-terminal kinase (JNK)-mediated phosphorylation of SARM1 regulates NAD+ cleavage activity to inhibit mitochondrial respiration\|Here, we report that NAD+ cleavage activity of SARM1 is regulated by its own phosphorylation at serine 548. The phosphorylation of SARM1 was mediated by c-jun N-terminal kinase (JNK) under oxidative stress conditions, resulting in inhibition of mitochondrial respiration concomitant with enhanced activity of NAD+ cleavage. Nonphosphorylatable mutation of Ser-548 or treatment with a JNK inhibitor decreased SARM1 activity.	SIGNOR-275554
O14656	O95295	1	binding	up-regulates activity	0.423	In the present study, we used yeast two-hybrid analysis to identify a new binding partner of torsinA, the SNARE-associated protein snapin. We have reported that snapin shows a robust interaction with wild type and mutant torsinA. we have demonstrated that this portion of torsinA and/or the adjacent linker region has the additional role of recruiting snapin. we found that snapin, which binds SNAP-25 (synaptosome-associated protein of 25,000 Da) and enhances the association of the SNARE complex with synaptotagmin, is an interacting partner for both wild type and mutant torsinA.	SIGNOR-261170
Q13315	Q92945	1	phosphorylation	up-regulates	0.423	The atm kinase directly binds to and phosphorylates ksrp, leading to enhanced interaction between ksrp and pri-mirnas and increased ksrp activity in mirna processing	SIGNOR-172127
P49411	Q9H1Y0	1	binding	down-regulates activity	0.423	PINK1 interacts with the autophagy effector TUFm and phosphorylates TUFm at Ser222. These results indicated that p222-hTUFm sequestered more monomer Atg5 and reduced the conjugated Atg5-Atg12 complex to subdue mitophagy.	SIGNOR-266383
P24941	P08047	1	phosphorylation	up-regulates activity	0.423	Mutation of Sp1 Ser59 abrogates the cyclin ACDK augmentation of Sp1-dependent transcriptional transactivation	SIGNOR-248232
P31749	Q8TDD2	1	phosphorylation	up-regulates	0.423	Akt, a member of the ser-ine/threonine-specific protein kinase, was found to phosphorylate osx and dlx5	SIGNOR-252514
Q9H2X6	O00257	1	phosphorylation	up-regulates activity	0.423	In addition, HIPK2 phosphorylates Pc2 at several sites, including threonine 495.	SIGNOR-278484
P17612	Q13131	1	phosphorylation	down-regulates activity	0.423	These agents also enhanced phosphorylation of alpha-Ser(485/491) by the cAMP-dependent protein kinase. AMPK alpha-Ser(485/491) phosphorylation was necessary but not sufficient for inhibition of AMPK activity in response to forskolin/isobutylmethylxanthine.	SIGNOR-256112
Q7Z6Z7	P04198	1	ubiquitination	down-regulates quantity by destabilization	0.423	HUWE1 ubiquitinates and directs MYCN degradation to the proteasome.	SIGNOR-278750
O96017	P06400	1	phosphorylation	up-regulates activity	0.423	Phosphorylation of prb at ser612 by chk1/2 leads to a complex between prb and e2f-1 after dna damageprb inhibits cell cycle progression through interactions with the e2f family of transcription factors. Here, we report that dna damage induced not only the dephosphorylation of prb at cdk phosphorylation sites and the binding of prb to e2f-1, but also the phosphorylation of prb at ser612. Phosphorylation of prb at ser612 enhanced the formation of a complex between prb and e2f-1	SIGNOR-153908
P07949	P28482	1	phosphorylation	up-regulates	0.423	We hypothesized that ret could directly phosphorylate fak and erk. erk 2 could be phosphorylated at y187 (y204 in erk1).	SIGNOR-140294
Q96GD4	P08670	1	phosphorylation	down-regulates	0.423	By identifying eight aurora-b phosphorylation sites on vimentin in vitro, we have demonstrated that vimentin-ser-72 is an in vitrophosphorylation site of aurora-b. in vitro analyses revealed that aurora-b phosphorylates vimentin at approximately 2 mol phosphate/mol of substrate for 30 min and that this phosphorylation dramatically inhibits vimentin filament formation.	SIGNOR-96057
Q96EB6	P46531	1	deacetylation	down-regulates	0.423	The acetylation marks on notch1-icd are removed by the deacetylase sirt1, suggesting that both deacetylation of notch1-icd and of histones inhibit notch signaling.	SIGNOR-195333
Q7Z6E9	Q8NAP3	1	ubiquitination	down-regulates quantity by destabilization	0.423	Thus, RBBP6 induces ZBTB38 protein degradation, and this depends on the activity of the proteasome.We next tested whether RBBP6 might directly ubiquitinate ZBTB38.\|We show that ZBTB38 is directly ubiquitinated by RBBP6 in human and mouse cells, in a process that is independent of p53 and MDM2, and leads to proteasomal degradation.	SIGNOR-278594
P29317	P07947	1	phosphorylation	up-regulates activity	0.423	EphA2 interacts with YES1 and phosphorylates YES1 at Tyr426 site.	SIGNOR-277556
P17612	P19429	1	phosphorylation	up-regulates activity	0.423	Phosphorylation at ser 23/24 (e.g., by pka or pkg) results in reduction in myofilament ca2+ sensitivity and an increase in crossbridge cycling rate, leading to acceleration of relaxation and an increase in power output but a reduced economy of contraction. Conversely, phosphorylation at ser 43/45 (by pkc) is associated with reduced maximum ca2+-activated force and decreased crossbridge cycling rates, which are likely to reduce power output and delay relaxation, with an increased economy of contraction.	SIGNOR-134605
P01009	P00734	1	binding	down-regulates activity	0.423	Alpha1PI, historically known as alpha1-antitrypsin, is a 51 kDa, 394 amino acid glycoprotein, synthesized in the liver, circulating at c. 1.3 mg mL-1 with a half-life of 4.5 days	SIGNOR-263524
P49841	O43623	1	phosphorylation	down-regulates activity	0.423	GSK3beta controls epithelial-mesenchymal transition and tumor metastasis by CHIP mediated degradation of Slug.\|Phosphorylation of Slug by GSK3beta promotes CHIP binding and ubiquitin mediated proteolysis.	SIGNOR-279414
Q16827	P55072	1	dephosphorylation	down-regulates activity	0.423	An important aspect of this study is that tyrosine dephosphorylation of VCP by PTPRO sensitizes HepG2 cells to Doxorubicin, a chemotherapeutic drug commonly used for a variety of cancers.	SIGNOR-277063
P27361	Q14247	1	phosphorylation	up-regulates	0.422	Cortactin is regulated by multiple phosphorylation events, including phosphorylation of s405 and s418 by extracellular regulated kinases (erk)1/2. Erk1/2 phosphorylation of cortactin has emerged as an important positive regulatory modification, enabling cortactin to bind and activate the arp2/3 regulator neuronal wiskott-aldrich syndrome protein (n-wasp), promoting actin polymerization and enhancing tumor cell movement.	SIGNOR-165212
O14757	P06400	1	phosphorylation	up-regulates activity	0.422	These results suggest that ser612 is phosphorylated by chk1/2 after dna damage, leading to the formation of prb-e2f-1. phosphorylation of prb at ser612 enhanced the formation of a complex between prb and e2f-1	SIGNOR-153904
P35452	O00470	1	binding	up-regulates activity	0.422	We now show that the Hoxa-9 protein physically interacts with Meis1 proteins. Hox proteins from the other AbdB-like paralogs, Hoxa-10, Hoxa-11, Hoxd-12, and Hoxb-13, also form DNA binding complexes with Meis1b. DNA binding complexes formed by Meis1 with Hox proteins dissociate much more slowly than DNA complexes with Meis1 alone, suggesting that Hox proteins stabilize the interactions of Meis1 proteins with their DNA targets.	SIGNOR-241232
P49674	P46937	1	phosphorylation	down-regulates	0.422	Phosphorylation of YAP (S381) and TAZ (S311) by Lats1/2 primes subsequent phosphorylation events by Casein Kinase 1 (CK1d/e); this sequential phosphorylation results in recruitment of b-transducin repeat-containing proteins (b-TRCP; a subunit of the SCF ubiquitin E3 ligase) and consequently leads to degradation of YAP/TAZ	SIGNOR-201170
P27361	Q9NZQ3	1	phosphorylation	up-regulates	0.422	Spin90 was phosphorylated by erk1, which was, itself, activated by cell adhesion and platelet-derived growth factor. Such phosphorylation of spin90 likely promotes the interaction of the spin90.betapix.wasp complex and nck	SIGNOR-118747
P42574	P25963	1	cleavage	up-regulates quantity by stabilization	0.422	The cell-death protease cpp32 (caspase-3) in vitro specifically cleaved chicken and human ikappab-alpha at a conserved asp-ser sequence.Therefore, cleavage of I_B-_ by a CPP32-like protease could create what is sometimes called a super-repressor form of I_B-_ (20). That is, cleavage by CPP32 would block the ability of I_B-_ to undergo signal-induced degradation by removing the sites of signal-induced ubiquitination and by likely disrupting the ability of I_B-_ to become phosphorylated at critical Ser residues.	SIGNOR-51936
P68400	P0DP23	1	phosphorylation	down-regulates activity	0.422	Phosphorylation of CaM at four sites by CK2 was found to follow a sequential order, with Ser81 as the first, Thr79 as the second, and Ser101 or Thr117 as the third.	SIGNOR-266355
Q9BXY4	P31431	1	binding	up-regulates	0.422	Here, we show that rspo3 binds syndecan 4 (sdc4) and that together they activate wnt/pcp signaling.	SIGNOR-172756
P20339	Q99570	1	binding	up-regulates activity	0.422	Vps34 PI 3-kinase activity18 is stimulated by complex formation with the protein kinase Vps15\|Rab5GTP binds Vps15, enhancing Vps34 activity	SIGNOR-260708
P07288	P12272	1	cleavage	down-regulates activity	0.422	Our study demonstrates that PTHrP is a substrate for PSA. The cleavage of the amino-terminal portion of PTHrP completely disrupts its ability to interact with the PTH/PTHrP receptor and thus inhibits its PTH-like activity. \| Our data show that PSA proteolytically cleaves PTHrP (1-34) after either residue 22 or 23, generating three peptide fragments.	SIGNOR-270547
Q16827	P12931	1	dephosphorylation	down-regulates activity	0.422	SRC activation triggered by loss of PTPRO leads to c-CBL degradation.\|These data corroborate that PTPRO directly dephosphorylates SRC at Y416.	SIGNOR-277004
P43657	O95837	1	binding	up-regulates activity	0.422	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257212
P06493	Q9Y2I6	1	phosphorylation	down-regulates quantity by destabilization	0.422	In this study, we show that Nlp can be phosphorylated by cell cycle protein kinase Cdc2/cyclin B1. The phosphorylation sites of Nlp are mapped at Ser185 and Ser589. the phosphorylation at the site Ser589 by Cdc2/cyclin B1 plays an important role in Nlp protein stability probably due to its effect on protein degradation.	SIGNOR-259831
Q8IW41	Q12778	1	phosphorylation	up-regulates activity	0.422	The kinase MK5 phosphorylates and activates Foxo1 at serine 215, and this modification is required for Foxo1 to induce Rag transcription.	SIGNOR-280037
O00192	P12830	1	binding	up-regulates quantity by stabilization	0.422	To clarify the role of p120 in mammalian cells, we have knocked down p120 with siRNA in cells expressing epithelial (E-), placental (P-), neuronal (N-), and vascular endothelial (VE-) cadherins. We report that each of these cadherins, as well as α- and β-catenins, were rapidly degraded in the absence of p120, resulting in loss of cell–cell adhesion. The effect was clearly dose dependent, indicating that p120 expression levels may directly determine cadherin levels. Degradation of p120-uncoupled cadherin occurred after its arrival at the surface, indicating that p120 regulates cadherin turnover at the level of internalization or recycling. p120 homologues ARVCF and δ-catenin could substitute for p120, so at least one family member is likely required to maintain adhesion. Thus, cadherin complexes are rapidly turned over and degraded in mammalian cells in the absence of direct interaction with p120 or a p120 family member.	SIGNOR-252133
P02679	P04004	1	binding	down-regulates activity	0.422	Fibrinogen y-chain carboxyterminal (GQQHHLGGAKQAGDV) peptides inhibit fibrinogen, fibronectin (Fn), vitronectin, and von Willebrand factor (vWF) binding to the platelet glycoprotein Ilb-Illa complex (GP lIbII1a).	SIGNOR-251969
P43405	Q02548	1	phosphorylation	down-regulates activity	0.422	PAX5 tyrosine phosphorylation by SYK co-operatively functions with its serine phosphorylation to cancel the PAX5-dependent repression of BLIMP1: A mechanism for antigen-triggered plasma cell differentiation.	SIGNOR-269084
Q96SB3	Q13009	1	binding	up-regulates quantity	0.422	Spinophilin binding promotes the plasma membrane localization of Tiam1 and enhances the ability of Tiam1 to activate p70 S6 kinase.	SIGNOR-269175
P23760	P50221	1	binding	up-regulates activity	0.422	We show that Mox1 and Mox2 proteins are capable of interacting with Pax1 and Pax3. We propose that the Mox family of homeodomain proteins participates in the molecular signaling network regulating the diverse events of somite development through the physical interaction with the Pax1 and Pax3 members of the Pax family.	SIGNOR-222235
Q9BYF1	Q9ULZ1	1	cleavage	up-regulates activity	0.422	ACE2 hydrolyzes the hormone apelin-13 with high catalytic efficiency and cleaves apelin-36, whose C-terminal 13 amino acids are identical to those of apelin-13.	SIGNOR-256316
O15054	Q15306	1	transcriptional regulation	up-regulates quantity by expression	0.422	JMJD3 seems to function by controlling expression of the transcription factor IRF4, which in turn is required for M2 polarization of macrophages in vitro and in vivo. Although this pathway is strongly supported by genetic.	SIGNOR-249540
O15197	P29317	1	binding	down-regulates activity	0.422	EphB6 is frequently silenced in invasive and metastatic cancers; however, its role in cancer progression is poorly understood. Here we show that EphB6 interacts with EphA2 and suppresses EphA2-mediated promotion of anoikis resistance in MCF7 breast cancer cells.	SIGNOR-273853
Q9UNW8	P50148	1	binding	up-regulates activity	0.422	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257341
Q96S53	P60981	1	phosphorylation	down-regulates activity	0.422	The present study provides evidence that TESK2 can phosphorylate cofilin and ADF specifically at Ser-3. Since actin-depolymerizing and -severing activities of cofilin/ADF are abrogated by phosphorylation at Ser-3, TESK2 seems to play an important role in actin filament dynamics by inhibiting cofilin/ADF activity.	SIGNOR-246707
Q13191	P08069	1	ubiquitination	down-regulates quantity by destabilization	0.422	The ubiquitin ligase Cbl-b also ubiquitinated and degraded IGF-IR and inhibited the Akt/ERK-miR-200c-ZEB2 axis, leading to the repression of IGF-I-induced EMT.	SIGNOR-278607
Q9Y6B2	Q09472	1	binding	down-regulates activity	0.421	Here, we show that EID-1 is a potent inhibitor of differentiation and link this activity to its ability to inhibit p300 (and the highly related molecule, CREB-binding protein, or CBP) histone acetylation activity.	SIGNOR-253379
Q86X55	P23759	1	methylation	up-regulates	0.421	Carm1 specifically methylates Pax7 at multiple arginine residues in the N terminus of Pax7	SIGNOR-255898
P48730	P46937	1	phosphorylation	down-regulates	0.421	LATS1/2-mediated phosphorylation of a conserved serine in this region (Ser311 in human TAZ; Ser397 in human YAP) primes for further phosphorylation by CK1_/_ kinases (Ser314 on human TAZ; Ser400/403 in human YAP)	SIGNOR-230738
P12931	P20701	1	phosphorylation	down-regulates activity	0.421	PTKs of the JAK and SRC families have a regulatory role in LFA-1 affinity triggering, with JAKs showing a positive role (3), whereas SRCs possibly have a negative role.	SIGNOR-254741
Q9ULZ2	P42229	1	binding	up-regulates activity	0.421	STAP-1 was tyrosine-phosphorylated by activated c-kit. An in vitro binding assay suggested that the STAP-1 SH2 domain interacted with several tyrosine-phosphorylated proteins including c-kit and STAT5. These suggest that STAP-1 functions as an adaptor molecule downstream of c-kit in hematopoietic stem cells.	SIGNOR-261821
Q15139	Q14247	1	phosphorylation	down-regulates	0.421	Pkd phosphorylates cortactin in vitro and in vivo at serine 298 thereby generating a 14-3-3 binding motif. In vitro, a phosphorylation-deficient cortactin-s298a protein accelerated vca-arp-cortactin-mediated synergistic actin polymerization and showed reduced f-actin binding	SIGNOR-164756
Q9UNE7	P55036	1	polyubiquitination	down-regulates quantity by destabilization	0.421	S5a/Rpn10 is a ubiquitin (Ub)-binding protein that is a subunit of the 26S proteasome but also exists free in the cytosol. It binds poly-Ub chains through its two Ub-interacting motifs (UIMs). We discovered that, unlike typical substrates of Ub ligases (E3s), S5a can be ubiquitinated by all E3s tested including multimeric and monomeric Ring finger E3s (MuRF1, Siah2, Parkin, APC, and SCF(betaTRCP1)), the U-box E3, CHIP, and HECT domain E3s (E6AP and Nedd4) when assayed with UbcH5 or related Ub-conjugating enzymes.The short half-life of S5a presumably is because of the presence of the UIM domain and reflects the ubiquitination of free S5a by many E3s.	SIGNOR-272752
P36888	P48735	1	phosphorylation	down-regulates activity	0.421	FLT3 promotes mIDH2 acetylation through Y107 phosphorylation of mIDH2 that enhances ACAT1 recruitment,	SIGNOR-267632
Q9NX95	Q16623	1	relocalization	up-regulates activity	0.421	Conventional kinesin I heavy chain binds to syntabulin and associates with syntabulin-linked syntaxin vesicles in vivo. These findings suggest that syntabulin functions as a linker molecule that attaches syntaxin-cargo vesicles to kinesin I, enabling the transport of syntaxin-1 to neuronal processes.	SIGNOR-264812
P60484	P08047	1	dephosphorylation	down-regulates activity	0.421	Moreover, PTEN downregulates p75NTR expression by decreasing DNA-binding activity of Sp1 .\|PTEN dephosphorylates the Sp1 transcription factor , the phosphorylation status of which directly impacts its ability to bind to some DNA promoter regions , .	SIGNOR-277119
P06493	Q9UKX7	1	phosphorylation	down-regulates	0.421	These results suggest that both ERK and Cdk1 directly phosphorylate Nup50 at Ser221 in intact cells\|Notably, erk phosphorylation of the fg repeat region of nup50 reduced its affinity for importin-beta family proteins, importin-beta and transportin.	SIGNOR-188061
O00303	P46531	1	deubiquitination	up-regulates	0.421	The activated form of notch needs to be deubiquitinated before being processed by the gamma-secretase activity and entering the nucleus, where it fulfills its transcriptional function. The enzyme accounting for this deubiquitinase activity is eif3f, known so far as a translation initiation factor.	SIGNOR-170158
P19544	P00797	1	transcriptional regulation	down-regulates quantity by repression	0.421	Here, we show that a splice variant of the Wilms' tumor protein lacking three amino acids WT1(-KTS) suppresses renin gene transcription	SIGNOR-252296
P68400	P48426	1	phosphorylation	up-regulates	0.421	Here, we demonstrate the partial purification of a protein kinase that phosphorylates the type iialpha pip kinase at a single site unique to that isoform - ser304. This kinase was identified as protein kinase ck2 (formerly casein kinase 2). Mutation of ser304 to aspartate to mimic its phosphorylation had no effect on pip kinase activity, but promoted both redistribution of the green fluorescent protein (gfp)-tagged enzyme in hela cells from the cytosol to the plasma membrane, and membrane ruffling.	SIGNOR-71014
Q9UKC9	P30279	1	binding	down-regulates quantity by destabilization	0.421	F-box protein FBXL2 targets cyclin D2 for ubiquitination and degradation to inhibit leukemic cell proliferation. Purified SCF complex components were incubated with V5-cyclin D2 and the full complement of ubiquitination reaction components (second lane from left) showing polyubiquitinated cyclin D2.	SIGNOR-272006
P68400	Q13563	1	phosphorylation	up-regulates	0.421	Ser(812) can be phosphorylated by ck2 in vitro and substitution s812a results in failure to incorporate phosphate in cultured epithelial cells.	SIGNOR-121572
Q8WTR2	P45983	1	dephosphorylation	down-regulates	0.421	Skrp1 was highly specific for c-jun n-terminal kinase (jnk) in vitro and effectively suppressed the jnk activation in response to tumor necrosis factor alpha or thapsigargin skrp1 does not bind directly to its target jnk, but co-precipitation of skrp1 with the mapk kinase mkk7, a jnk activator, was found in vitro and in vivo.	SIGNOR-117260
Q12923	O00506	1	dephosphorylation	down-regulates activity	0.421	To investigate dephosphorylation of CCM3 by FAP-1, phosphorylated GST-CCM3 was incubated with cdFAP-1, and reactions were analyzed by autoradiography. Again, GST-STK25 phosphorylated GST-CCM3 and possessed autophosphorylation activity. cdFAP-1 of 0.005 U were sufficient to dephosphorylate GST-CCM3 as well as the kinase GST-STK25.\|More recently, the Golgi matrix protein GM130 was shown to function as a scaffold protein for STK25 and to activate STK25 through stimulation of autophosphorylation.	SIGNOR-248711
P12931	Q8NEB9	1	phosphorylation	up-regulates activity	0.42	Given that VPS34 is activated by Src mediated tyrosine phosphorylation, we next determined if VPS34 was tyrosine phosphorylated following insulin treatment.\|These data indicate that VPS34 is an effector of insulin-mediated signal transduction and that Src phosphorylation of VPS34 is required for this function.	SIGNOR-278456
P17612	P54646	1	phosphorylation	down-regulates	0.42	Pka associates with and phosphorylates ampk?1 At ser-173 to impede threonine thr-172 phosphorylation and thus activation of ampk1 by lkb1 in response to lipolytic signals	SIGNOR-161860
P12931	O75553	1	phosphorylation	up-regulates activity	0.42	Dab1 is rapidly phosphorylated when neurons isolated from embryonic brains are stimulated with Reelin, and several tyrosines have been implicated in this response. Mice with phenylalanine substitutions of all five tyrosines (Tyr(185), Tyr(198), Tyr(200), Tyr(220), and Tyr(232)) exhibit a reeler phenotype, implying that tyrosine phosphorylation is critical for Dab1 function. Here we report that, although Src can phosphorylate all five tyrosines in vitro, Tyr(198) and Tyr(220) represent the major sites of Reelin-induced Dab1 phosphorylation in embryonic neurons.	SIGNOR-247080
P31751	Q6ZWJ1	1	phosphorylation	down-regulates activity	0.42	Akt2 phosphorylates Synip to regulate docking and fusion of GLUT4-containing vesicles. These data demonstrate that insulin activation of Akt2 specifically regulates the docking/fusion step of GLUT4-containing vesicles at the plasma membrane through the regulation of Synip phosphorylation and Synip-Syntaxin4 interaction.Thus, our data demonstrate that insulin-stimulated Akt2-dependent phosphorylation of Synip on serine residue 99 results in reduced binding interactions between Synip and Syntaxin4.	SIGNOR-262635

P62837

Q9C026

1

binding

up-regulates activity

0.425

Collectively, these results indicated that TRIM9 is an E3 ligase for its self-ubiquitination and that the ubiquitination of TRIM9 likely serves as a signal for proteasomal degradation. As shown in Fig. 1A, TRIM9 was ubiquitinated by itself when incubated with UbcH5b. In contrast, ubiquitination was observed when incubated with other E2 enzymes. These results suggest that TRIM9 cooperates with UbcH5b for its self-ubiquitination. N

SIGNOR-271420

P53350

P78527

2

phosphorylation

up-regulates activity

0.425

Moreover, PLK1 phosphorylates DNA-PKcs directly on Ser 3205 invitro, suggesting that DNA-PKcs Ser 3205 is a direct target of PLK1 in mitosis.

SIGNOR-278188

Q9Y2G2

P55211

1

binding

down-regulates

0.425

Tucan is a recently identified card-containing protein that can complex with caspase-9 and prevent cytochrome c-induced caspase activation.

SIGNOR-146663

P00441

P21796

1

binding

down-regulates activity

0.425

Misfolded Mutant SOD1 Directly Inhibits VDAC1 Conductance in a Mouse Model of Inherited ALS|With conformation-specific antibodies, we now demonstrate that misfolded mutant SOD1 binds directly to the voltage-dependent anion channel (VDAC1), an integral membrane protein imbedded in the outer mitochondrial membrane.

SIGNOR-262798

O15194

P84022

1

dephosphorylation

up-regulates activity

0.424

Dephosphorylation of Smad2/3 Linkers by SCP2 and SCP3|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity

SIGNOR-248306

P36888

O75874

1

phosphorylation

up-regulates activity

0.424

Moreover, in an in vitro kinase assay, purified recombinant FLT3 (rFLT3) phosphorylated recombinant IDH2 R140Q mutant but did not alter its catalytic activity (Figure 1C), whereas rFLT3 phosphorylated mIDH1 protein and enhanced its catalytic activity

SIGNOR-267630

Q96PY6

P21796

1

phosphorylation

down-regulates

0.424

Nek1 phosphorylates vdac1 on ser193. Wild-type vdac1 assumes an open configuration, but closes and prevents cytochrome c efflux when phosphorylated by nek1. A vdac1-ser193ala mutant, which cannot be phosphorylated by nek1 under identical conditions, remains open and constitutively allows cytochrome c efflux.

SIGNOR-164222

Q16236

Q9UPY5

1

transcriptional regulation

up-regulates quantity by expression

0.424

NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification. NFE2L2 directly binds to the promoter region of SLC7A11, leading to increased expression of this transporter, which in turn contributes to the resistance to ferroptosis and to radiotherapy

SIGNOR-279867

Q00987

Q9Y6B2

1

polyubiquitination

down-regulates quantity by destabilization

0.424

Degradation of EID-1 occurs via ubiquitin-dependent proteolysis and correlates with MDM2 binding. These results are consistent with a model wherein destruction of EID-1 is linked to its ability to interact with MDM2 via either p300 or pRB.

SIGNOR-272582

P23443

P36956

1

phosphorylation

up-regulates activity

0.424

Besides promoting protein synthesis, S6K1 also phosphorylates and activates sterol regulatory element binding protein 1 and 2 (SREBP and SREBP2), which promotes de novo lipid synthesis that is critical for cell growth and proliferation.|Besides promoting protein synthesis, S6K1 also phosphorylates and activates sterol regulatory element-binding protein 1 and 2 (SREBP and SREBP2), which promotes de novo lipid synthesis that is critical for cell growth and proliferation ( xref ).

SIGNOR-280120

P68400

Q9UNN4

1

phosphorylation

up-regulates activity

0.424

ALF was able to stabilize the binding of TBP to DNA, but it could not stabilize TBP mutants A184E, N189E, E191R, and R205E nor could it facilitate binding of the TBP-like factor TRF2/TLF to a consensus TATA element. However, phosphorylation of ALF with casein kinase II resulted in the partial restoration of complex formation using mutant TBPs. | Because the residues involved (Ser-280, Ser-281, Ser-316, and Ser-321) are conserved in ALF (Ser-356, Ser-357, Ser-418, and Ser-423), we tested whether its activity might also be affected by this modification. We first showed that ALF and TFIIAα/β polypeptides incubated with casein kinase II and [γ-32P]ATP could be labeled.

SIGNOR-250873

P53350

Q13526

1

phosphorylation

up-regulates

0.424

Here we demonstrate that ser-65 in pin1 is the major site for plk1-specific phosphorylation, and the polo-box domain of plk1 is required for this phosphorylation. Interestingly, the phosphorylation of pin1 by plk1 does not affect its isomerase activity but rather is linked to its protein stability. pin1 is ubiquitinated in hela s3 cells, and substitution of glu for ser-65 reduces the ubiquitination of pin1.

SIGNOR-139919

P00519

Q9BX66

1

phosphorylation

up-regulates activity

0.424

We have here identified Tyr360 in CAP as a major phosphorylation site by c-Abl, although Tyr 632 also might contribute since its substitution in combination with the Y360F mutation reduced the phosphorylation of CAP to a very low level. Y360 in CAP is the major phosphorylation site of c-Abl. Since Tyr326 was not a major c-Abl phosphorylation site, we sought to identify a putative other kinase that might be involved in the phosphorylation of Y326 in CAP.

SIGNOR-278153

Q9HBW1

P78352

1

binding

up-regulates activity

0.424

A possible function for the NGL–PSD-95 interaction is to couple trans-synaptic adhesion events to the recruitment of PSD-95 and other PSD-95-associated postsynaptic proteins. PSD-95 and liprin-α may be key synaptic scaffolding proteins that couple trans-synaptic adhesions to the assembly of synaptic proteins/vesicles

SIGNOR-264051

O14595

P84022

1

dephosphorylation

up-regulates activity

0.424

Dephosphorylation of Smad2/3 Linkers by SCP2 and SCP3|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity

SIGNOR-248293

Q05655

O15162

1

phosphorylation

up-regulates

0.424

Following the induction of apoptosis, however, phosphorylation of serine residues decreased and it increased on threonine, consistent with the predicted pkc phosphorylation site at thr-161. Transfection of cho cells with scramblase and pkc_, but not scramblase or pkc_ alone, increased scramblase activity

SIGNOR-76904

Q08345

P30408

1

binding

up-regulates activity

0.424

Gao et al have demonstrated that in metastatic breast cancer cell, DDR1 interacts with cell surface Transmembrane 4 L Six Family Member 1 (TM4SF1) and regulates tumor dormancy and reactivation [3]. The interaction between DDR1 and TM4SF1 is collagen dependent and control Protein Kinase C Alpha (PKCa) mediated downstream JAK-STAT signaling pathway [3] (Figure 3). Interestingly the data also showed that TM4SF1 failed to interact with DDR2.

SIGNOR-272400

Q8TEV9

O75385

1

binding

down-regulates activity

0.424

While focusing on the role of SMCR8 during autophagy initiation, we found that kinase activity and gene expression of ULK1 are increased upon SMCR8 depletion.

SIGNOR-252029

P08581

Q03135

1

phosphorylation

up-regulates activity

0.424

Findings obtained using SNU-449 cells suggested that c-Met positively regulated CAV1 activity.|Inhibition of c-Met activation abolished phosphorylation of CAV1 on Tyrosine 14.

SIGNOR-279080

P49841

P60484

1

phosphorylation

down-regulates activity

0.424

Gsk3beta Phosphorylates pten at thr-366 in intact cells phosphorylation of pten at thr-366 reduces the activity of pten in cells

SIGNOR-236641

P02452

Q16832

1

binding

up-regulates activity

0.424

The Discoidin Domain Receptors (DDRs) constitute a unique set of receptor tyrosine kinases that signal in response to collagen.|Consistent with this view128, we showed that ectopic expression of DDR1b or DDR2 in HT1080 cells elicited a potent growth inhibitory effect only when the cells were cultured on 2D or 3D COL1 matrices, in agreement with previous studies in melanoma48, breast cancer76,78, and lung cancer cells74,75.

SIGNOR-272342

P29376

P29353

1

phosphorylation

up-regulates

0.424

Recently, we demonstrated that ltk utilizes shc and irs-1 as two major substrates and while both equally activate the ras pathway, only irs-1 suppresses apoptosis of hematopoietic cells.

SIGNOR-49625

Q9H2X6

Q92793

1

phosphorylation

up-regulates activity

0.424

Moreover, we show that HIPK2 strongly potentiates the transcriptional activity of CREB-binding protein.|We show that HIPK2 interacts with and phosphorylates several regions of CBP.

SIGNOR-279191

P25116

P09471

1

binding

up-regulates activity

0.424

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257011

Q14192

Q9NYA1

1

binding

down-regulates activity

0.424

FHL2/SLIM3 decreases cardiomyocyte survival by inhibitory interaction with sphingosine kinase-1.

SIGNOR-237775

Q9GZV5

P43699

1

binding

up-regulates

0.424

Taz also binds to the transcription factor ttf-1 that is involved in formation and differentiation of the lungs and respiratory epithelia, and stimulates the production of pulmonary surfactant.

SIGNOR-143472

P31749

O75376

1

phosphorylation

down-regulates

0.424

Akt-induced phosphorylation of n-cor at serine 1450 contributes to its misfolded conformational dependent loss (mcdl) in acute myeloid leukemia of the m5 subtype.

SIGNOR-198913

P00519

P37840

1

phosphorylation

up-regulates quantity

0.424

C-Abl interacts with alpha-synuclein and phosphorylates alpha-synuclein at Y39 (XREF_FIG) .

SIGNOR-279582

P00519

Q14247

1

phosphorylation

up-regulates activity

0.424

Because phosphorylation by c-Abl augments nmMLCK-cortactin interaction to a greater degree than does pp60src phosphorylation, it is likely that phosphorylation sites on nmMLCK unique to c-Abl (i.e., other than Y464 and Y846) are responsible for this enhanced protein-protein interaction.|Moreover, our data indicate that cortactin is itself rapidly phosphorylated on Y486 by c-Abl in EC after S1P (Figure 9).

SIGNOR-278504

Q7KZI7

P46939

1

phosphorylation

up-regulates

0.424

Par-1b, interacts with the utrophin-dg complex, and positively regulates the interaction between utrophin and dg. Ser1258 within r9 is specifically phosphorylated by par-1b.

SIGNOR-161915

P31749

P54578

1

phosphorylation

up-regulates activity

0.424

Phosphorylation and activation of ubiquitin-specific protease-14 by Akt regulates the ubiquitin-proteasome system|These results suggested S432 as a major and S143 as a minor phosphorylation site of Akt.

SIGNOR-265056

Q70Z35

P60953

1

guanine nucleotide exchange factor

up-regulates activity

0.423

We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).

SIGNOR-260572

Q00534

P05412

1

phosphorylation

up-regulates quantity

0.423

CDK6 additionally induced c-Jun phosphorylation, but did not activate JNK, as determined by examining JNK phosphorylation at various time-points.|CDK6 upregulates c-Jun expression.

SIGNOR-280222

Q9Y243

Q9UKV8

1

phosphorylation

up-regulates

0.423

Phosphorylation of argonaute 2 at serine-387 facilitates its localization to processing bodies, akt3-mediated phosphorylation of ago2 is a molecular switch between target mrna cleavage and translational repression activities of ago2

SIGNOR-178416

P45983

Q6SZW1

1

phosphorylation

down-regulates activity

0.423

C-Jun N-terminal kinase (JNK)-mediated phosphorylation of SARM1 regulates NAD+ cleavage activity to inhibit mitochondrial respiration|Here, we report that NAD+ cleavage activity of SARM1 is regulated by its own phosphorylation at serine 548. The phosphorylation of SARM1 was mediated by c-jun N-terminal kinase (JNK) under oxidative stress conditions, resulting in inhibition of mitochondrial respiration concomitant with enhanced activity of NAD+ cleavage. Nonphosphorylatable mutation of Ser-548 or treatment with a JNK inhibitor decreased SARM1 activity.

SIGNOR-275554

O14656

O95295

1

binding

up-regulates activity

0.423

In the present study, we used yeast two-hybrid analysis to identify a new binding partner of torsinA, the SNARE-associated protein snapin. We have reported that snapin shows a robust interaction with wild type and mutant torsinA. we have demonstrated that this portion of torsinA and/or the adjacent linker region has the additional role of recruiting snapin. we found that snapin, which binds SNAP-25 (synaptosome-associated protein of 25,000 Da) and enhances the association of the SNARE complex with synaptotagmin, is an interacting partner for both wild type and mutant torsinA.

SIGNOR-261170

Q13315

Q92945

1

phosphorylation

up-regulates

0.423

The atm kinase directly binds to and phosphorylates ksrp, leading to enhanced interaction between ksrp and pri-mirnas and increased ksrp activity in mirna processing

SIGNOR-172127

P49411

Q9H1Y0

1

binding

down-regulates activity

0.423

PINK1 interacts with the autophagy effector TUFm and phosphorylates TUFm at Ser222. These results indicated that p222-hTUFm sequestered more monomer Atg5 and reduced the conjugated Atg5-Atg12 complex to subdue mitophagy.

SIGNOR-266383

P24941

P08047

1

phosphorylation

up-regulates activity

0.423

Mutation of Sp1 Ser59 abrogates the cyclin ACDK augmentation of Sp1-dependent transcriptional transactivation

SIGNOR-248232

P31749

Q8TDD2

1

phosphorylation

up-regulates

0.423

Akt, a member of the ser-ine/threonine-specific protein kinase, was found to phosphorylate osx and dlx5

SIGNOR-252514

Q9H2X6

O00257

1

phosphorylation

up-regulates activity

0.423

In addition, HIPK2 phosphorylates Pc2 at several sites, including threonine 495.

SIGNOR-278484

P17612

Q13131

1

phosphorylation

down-regulates activity

0.423

These agents also enhanced phosphorylation of alpha-Ser(485/491) by the cAMP-dependent protein kinase. AMPK alpha-Ser(485/491) phosphorylation was necessary but not sufficient for inhibition of AMPK activity in response to forskolin/isobutylmethylxanthine.

SIGNOR-256112

Q7Z6Z7

P04198

1

ubiquitination

down-regulates quantity by destabilization

0.423

HUWE1 ubiquitinates and directs MYCN degradation to the proteasome.

SIGNOR-278750

O96017

P06400

1

phosphorylation

up-regulates activity

0.423

Phosphorylation of prb at ser612 by chk1/2 leads to a complex between prb and e2f-1 after dna damageprb inhibits cell cycle progression through interactions with the e2f family of transcription factors. Here, we report that dna damage induced not only the dephosphorylation of prb at cdk phosphorylation sites and the binding of prb to e2f-1, but also the phosphorylation of prb at ser612. Phosphorylation of prb at ser612 enhanced the formation of a complex between prb and e2f-1

SIGNOR-153908

P07949

P28482

1

phosphorylation

up-regulates

0.423

We hypothesized that ret could directly phosphorylate fak and erk. erk 2 could be phosphorylated at y187 (y204 in erk1).

SIGNOR-140294

Q96GD4

P08670

1

phosphorylation

down-regulates

0.423

By identifying eight aurora-b phosphorylation sites on vimentin in vitro, we have demonstrated that vimentin-ser-72 is an in vitrophosphorylation site of aurora-b. in vitro analyses revealed that aurora-b phosphorylates vimentin at approximately 2 mol phosphate/mol of substrate for 30 min and that this phosphorylation dramatically inhibits vimentin filament formation.

SIGNOR-96057

Q96EB6

P46531

1

deacetylation

down-regulates

0.423

The acetylation marks on notch1-icd are removed by the deacetylase sirt1, suggesting that both deacetylation of notch1-icd and of histones inhibit notch signaling.

SIGNOR-195333

Q7Z6E9

Q8NAP3

1

ubiquitination

down-regulates quantity by destabilization

0.423

Thus, RBBP6 induces ZBTB38 protein degradation, and this depends on the activity of the proteasome.We next tested whether RBBP6 might directly ubiquitinate ZBTB38.|We show that ZBTB38 is directly ubiquitinated by RBBP6 in human and mouse cells, in a process that is independent of p53 and MDM2, and leads to proteasomal degradation.

SIGNOR-278594

P29317

P07947

1

phosphorylation

up-regulates activity

0.423

EphA2 interacts with YES1 and phosphorylates YES1 at Tyr426 site.

SIGNOR-277556

P17612

P19429

1

phosphorylation

up-regulates activity

0.423

Phosphorylation at ser 23/24 (e.g., by pka or pkg) results in reduction in myofilament ca2+ sensitivity and an increase in crossbridge cycling rate, leading to acceleration of relaxation and an increase in power output but a reduced economy of contraction. Conversely, phosphorylation at ser 43/45 (by pkc) is associated with reduced maximum ca2+-activated force and decreased crossbridge cycling rates, which are likely to reduce power output and delay relaxation, with an increased economy of contraction.

SIGNOR-134605

P01009

P00734

1

binding

down-regulates activity

0.423

Alpha1PI, historically known as alpha1-antitrypsin, is a 51 kDa, 394 amino acid glycoprotein, synthesized in the liver, circulating at c. 1.3 mg mL-1 with a half-life of 4.5 days

SIGNOR-263524

P49841

O43623

1

phosphorylation

down-regulates activity

0.423

GSK3beta controls epithelial-mesenchymal transition and tumor metastasis by CHIP mediated degradation of Slug.|Phosphorylation of Slug by GSK3beta promotes CHIP binding and ubiquitin mediated proteolysis.

SIGNOR-279414

Q16827

P55072

1

dephosphorylation

down-regulates activity

0.423

An important aspect of this study is that tyrosine dephosphorylation of VCP by PTPRO sensitizes HepG2 cells to Doxorubicin, a chemotherapeutic drug commonly used for a variety of cancers.

SIGNOR-277063

P27361

Q14247

1

phosphorylation

up-regulates

0.422

Cortactin is regulated by multiple phosphorylation events, including phosphorylation of s405 and s418 by extracellular regulated kinases (erk)1/2. Erk1/2 phosphorylation of cortactin has emerged as an important positive regulatory modification, enabling cortactin to bind and activate the arp2/3 regulator neuronal wiskott-aldrich syndrome protein (n-wasp), promoting actin polymerization and enhancing tumor cell movement.

SIGNOR-165212

O14757

P06400

1

phosphorylation

up-regulates activity

0.422

These results suggest that ser612 is phosphorylated by chk1/2 after dna damage, leading to the formation of prb-e2f-1. phosphorylation of prb at ser612 enhanced the formation of a complex between prb and e2f-1

SIGNOR-153904

P35452

O00470

1

binding

up-regulates activity

0.422

We now show that the Hoxa-9 protein physically interacts with Meis1 proteins. Hox proteins from the other AbdB-like paralogs, Hoxa-10, Hoxa-11, Hoxd-12, and Hoxb-13, also form DNA binding complexes with Meis1b. DNA binding complexes formed by Meis1 with Hox proteins dissociate much more slowly than DNA complexes with Meis1 alone, suggesting that Hox proteins stabilize the interactions of Meis1 proteins with their DNA targets.

SIGNOR-241232

P49674

P46937

1

phosphorylation

down-regulates

0.422

Phosphorylation of YAP (S381) and TAZ (S311) by Lats1/2 primes subsequent phosphorylation events by Casein Kinase 1 (CK1d/e); this sequential phosphorylation results in recruitment of b-transducin repeat-containing proteins (b-TRCP; a subunit of the SCF ubiquitin E3 ligase) and consequently leads to degradation of YAP/TAZ

SIGNOR-201170

P27361

Q9NZQ3

1

phosphorylation

up-regulates

0.422

Spin90 was phosphorylated by erk1, which was, itself, activated by cell adhesion and platelet-derived growth factor. Such phosphorylation of spin90 likely promotes the interaction of the spin90.betapix.wasp complex and nck

SIGNOR-118747

P42574

P25963

1

cleavage

up-regulates quantity by stabilization

0.422

The cell-death protease cpp32 (caspase-3) in vitro specifically cleaved chicken and human ikappab-alpha at a conserved asp-ser sequence.Therefore, cleavage of I_B-_ by a CPP32-like protease could create what is sometimes called a super-repressor form of I_B-_ (20). That is, cleavage by CPP32 would block the ability of I_B-_ to undergo signal-induced degradation by removing the sites of signal-induced ubiquitination and by likely disrupting the ability of I_B-_ to become phosphorylated at critical Ser residues.

SIGNOR-51936

P68400

P0DP23

1

phosphorylation

down-regulates activity

0.422

Phosphorylation of CaM at four sites by CK2 was found to follow a sequential order, with Ser81 as the first, Thr79 as the second, and Ser101 or Thr117 as the third.

SIGNOR-266355

Q9BXY4

P31431

1

binding

up-regulates

0.422

Here, we show that rspo3 binds syndecan 4 (sdc4) and that together they activate wnt/pcp signaling.

SIGNOR-172756

P20339

Q99570

1

binding

up-regulates activity

0.422

Vps34 PI 3-kinase activity18 is stimulated by complex formation with the protein kinase Vps15|Rab5GTP binds Vps15, enhancing Vps34 activity

SIGNOR-260708

P07288

P12272

1

cleavage

down-regulates activity

0.422

Our study demonstrates that PTHrP is a substrate for PSA. The cleavage of the amino-terminal portion of PTHrP completely disrupts its ability to interact with the PTH/PTHrP receptor and thus inhibits its PTH-like activity. | Our data show that PSA proteolytically cleaves PTHrP (1-34) after either residue 22 or 23, generating three peptide fragments.

SIGNOR-270547

Q16827

P12931

1

dephosphorylation

down-regulates activity

0.422

SRC activation triggered by loss of PTPRO leads to c-CBL degradation.|These data corroborate that PTPRO directly dephosphorylates SRC at Y416.

SIGNOR-277004

P43657

O95837

1

binding

up-regulates activity

0.422

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257212

P06493

Q9Y2I6

1

phosphorylation

down-regulates quantity by destabilization

0.422

In this study, we show that Nlp can be phosphorylated by cell cycle protein kinase Cdc2/cyclin B1. The phosphorylation sites of Nlp are mapped at Ser185 and Ser589. the phosphorylation at the site Ser589 by Cdc2/cyclin B1 plays an important role in Nlp protein stability probably due to its effect on protein degradation.

SIGNOR-259831

Q8IW41

Q12778

1

phosphorylation

up-regulates activity

0.422

The kinase MK5 phosphorylates and activates Foxo1 at serine 215, and this modification is required for Foxo1 to induce Rag transcription.

SIGNOR-280037

O00192

P12830

1

binding

up-regulates quantity by stabilization

0.422

To clarify the role of p120 in mammalian cells, we have knocked down p120 with siRNA in cells expressing epithelial (E-), placental (P-), neuronal (N-), and vascular endothelial (VE-) cadherins. We report that each of these cadherins, as well as α- and β-catenins, were rapidly degraded in the absence of p120, resulting in loss of cell–cell adhesion. The effect was clearly dose dependent, indicating that p120 expression levels may directly determine cadherin levels. Degradation of p120-uncoupled cadherin occurred after its arrival at the surface, indicating that p120 regulates cadherin turnover at the level of internalization or recycling. p120 homologues ARVCF and δ-catenin could substitute for p120, so at least one family member is likely required to maintain adhesion. Thus, cadherin complexes are rapidly turned over and degraded in mammalian cells in the absence of direct interaction with p120 or a p120 family member.

SIGNOR-252133

P02679

P04004

1

binding

down-regulates activity

0.422

Fibrinogen y-chain carboxyterminal (GQQHHLGGAKQAGDV) peptides inhibit fibrinogen, fibronectin (Fn), vitronectin, and von Willebrand factor (vWF) binding to the platelet glycoprotein Ilb-Illa complex (GP lIbII1a).

SIGNOR-251969

P43405

Q02548

1

phosphorylation

down-regulates activity

0.422

PAX5 tyrosine phosphorylation by SYK co-operatively functions with its serine phosphorylation to cancel the PAX5-dependent repression of BLIMP1: A mechanism for antigen-triggered plasma cell differentiation.

SIGNOR-269084

Q96SB3

Q13009

1

binding

up-regulates quantity

0.422

Spinophilin binding promotes the plasma membrane localization of Tiam1 and enhances the ability of Tiam1 to activate p70 S6 kinase.

SIGNOR-269175

P23760

P50221

1

binding

up-regulates activity

0.422

We show that Mox1 and Mox2 proteins are capable of interacting with Pax1 and Pax3. We propose that the Mox family of homeodomain proteins participates in the molecular signaling network regulating the diverse events of somite development through the physical interaction with the Pax1 and Pax3 members of the Pax family.

SIGNOR-222235

Q9BYF1

Q9ULZ1

1

cleavage

up-regulates activity

0.422

ACE2 hydrolyzes the hormone apelin-13 with high catalytic efficiency and cleaves apelin-36, whose C-terminal 13 amino acids are identical to those of apelin-13.

SIGNOR-256316

O15054

Q15306

1

transcriptional regulation

up-regulates quantity by expression

0.422

JMJD3 seems to function by controlling expression of the transcription factor IRF4, which in turn is required for M2 polarization of macrophages in vitro and in vivo. Although this pathway is strongly supported by genetic.

SIGNOR-249540

O15197

P29317

1

binding

down-regulates activity

0.422

EphB6 is frequently silenced in invasive and metastatic cancers; however, its role in cancer progression is poorly understood. Here we show that EphB6 interacts with EphA2 and suppresses EphA2-mediated promotion of anoikis resistance in MCF7 breast cancer cells.

SIGNOR-273853

Q9UNW8

P50148

1

binding

up-regulates activity

0.422

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257341

Q96S53

P60981

1

phosphorylation

down-regulates activity

0.422

The present study provides evidence that TESK2 can phosphorylate cofilin and ADF specifically at Ser-3. Since actin-depolymerizing and -severing activities of cofilin/ADF are abrogated by phosphorylation at Ser-3, TESK2 seems to play an important role in actin filament dynamics by inhibiting cofilin/ADF activity.

SIGNOR-246707

Q13191

P08069

1

ubiquitination

down-regulates quantity by destabilization

0.422

The ubiquitin ligase Cbl-b also ubiquitinated and degraded IGF-IR and inhibited the Akt/ERK-miR-200c-ZEB2 axis, leading to the repression of IGF-I-induced EMT.

SIGNOR-278607

Q9Y6B2

Q09472

1

binding

down-regulates activity

0.421

Here, we show that EID-1 is a potent inhibitor of differentiation and link this activity to its ability to inhibit p300 (and the highly related molecule, CREB-binding protein, or CBP) histone acetylation activity.

SIGNOR-253379

Q86X55

P23759

1

methylation

up-regulates

0.421

Carm1 specifically methylates Pax7 at multiple arginine residues in the N terminus of Pax7

SIGNOR-255898

P48730

P46937

1

phosphorylation

down-regulates

0.421

LATS1/2-mediated phosphorylation of a conserved serine in this region (Ser311 in human TAZ; Ser397 in human YAP) primes for further phosphorylation by CK1_/_ kinases (Ser314 on human TAZ; Ser400/403 in human YAP)

SIGNOR-230738

P12931

P20701

1

phosphorylation

down-regulates activity

0.421

PTKs of the JAK and SRC families have a regulatory role in LFA-1 affinity triggering, with JAKs showing a positive role (3), whereas SRCs possibly have a negative role.

SIGNOR-254741

Q9ULZ2

P42229

1

binding

up-regulates activity

0.421

STAP-1 was tyrosine-phosphorylated by activated c-kit. An in vitro binding assay suggested that the STAP-1 SH2 domain interacted with several tyrosine-phosphorylated proteins including c-kit and STAT5. These suggest that STAP-1 functions as an adaptor molecule downstream of c-kit in hematopoietic stem cells.

SIGNOR-261821

Q15139

Q14247

1

phosphorylation

down-regulates

0.421

Pkd phosphorylates cortactin in vitro and in vivo at serine 298 thereby generating a 14-3-3 binding motif. In vitro, a phosphorylation-deficient cortactin-s298a protein accelerated vca-arp-cortactin-mediated synergistic actin polymerization and showed reduced f-actin binding

SIGNOR-164756

Q9UNE7

P55036

1

polyubiquitination

down-regulates quantity by destabilization

0.421

S5a/Rpn10 is a ubiquitin (Ub)-binding protein that is a subunit of the 26S proteasome but also exists free in the cytosol. It binds poly-Ub chains through its two Ub-interacting motifs (UIMs). We discovered that, unlike typical substrates of Ub ligases (E3s), S5a can be ubiquitinated by all E3s tested including multimeric and monomeric Ring finger E3s (MuRF1, Siah2, Parkin, APC, and SCF(betaTRCP1)), the U-box E3, CHIP, and HECT domain E3s (E6AP and Nedd4) when assayed with UbcH5 or related Ub-conjugating enzymes.The short half-life of S5a presumably is because of the presence of the UIM domain and reflects the ubiquitination of free S5a by many E3s.

SIGNOR-272752

P36888

P48735

1

phosphorylation

down-regulates activity

0.421

FLT3 promotes mIDH2 acetylation through Y107 phosphorylation of mIDH2 that enhances ACAT1 recruitment,

SIGNOR-267632

Q9NX95

Q16623

1

relocalization

up-regulates activity

0.421

Conventional kinesin I heavy chain binds to syntabulin and associates with syntabulin-linked syntaxin vesicles in vivo. These findings suggest that syntabulin functions as a linker molecule that attaches syntaxin-cargo vesicles to kinesin I, enabling the transport of syntaxin-1 to neuronal processes.

SIGNOR-264812

P60484

P08047

1

dephosphorylation

down-regulates activity

0.421

Moreover, PTEN downregulates p75NTR expression by decreasing DNA-binding activity of Sp1 .|PTEN dephosphorylates the Sp1 transcription factor , the phosphorylation status of which directly impacts its ability to bind to some DNA promoter regions , .

SIGNOR-277119

P06493

Q9UKX7

1

phosphorylation

down-regulates

0.421

These results suggest that both ERK and Cdk1 directly phosphorylate Nup50 at Ser221 in intact cells|Notably, erk phosphorylation of the fg repeat region of nup50 reduced its affinity for importin-beta family proteins, importin-beta and transportin.

SIGNOR-188061

O00303

P46531

1

deubiquitination

up-regulates

0.421

The activated form of notch needs to be deubiquitinated before being processed by the gamma-secretase activity and entering the nucleus, where it fulfills its transcriptional function. The enzyme accounting for this deubiquitinase activity is eif3f, known so far as a translation initiation factor.

SIGNOR-170158

P19544

P00797

1

transcriptional regulation

down-regulates quantity by repression

0.421

Here, we show that a splice variant of the Wilms' tumor protein lacking three amino acids WT1(-KTS) suppresses renin gene transcription

SIGNOR-252296

P68400

P48426

1

phosphorylation

up-regulates

0.421

Here, we demonstrate the partial purification of a protein kinase that phosphorylates the type iialpha pip kinase at a single site unique to that isoform - ser304. This kinase was identified as protein kinase ck2 (formerly casein kinase 2). Mutation of ser304 to aspartate to mimic its phosphorylation had no effect on pip kinase activity, but promoted both redistribution of the green fluorescent protein (gfp)-tagged enzyme in hela cells from the cytosol to the plasma membrane, and membrane ruffling.

SIGNOR-71014

Q9UKC9

P30279

1

binding

down-regulates quantity by destabilization

0.421

F-box protein FBXL2 targets cyclin D2 for ubiquitination and degradation to inhibit leukemic cell proliferation. Purified SCF complex components were incubated with V5-cyclin D2 and the full complement of ubiquitination reaction components (second lane from left) showing polyubiquitinated cyclin D2.

SIGNOR-272006

P68400

Q13563

1

phosphorylation

up-regulates

0.421

Ser(812) can be phosphorylated by ck2 in vitro and substitution s812a results in failure to incorporate phosphate in cultured epithelial cells.

SIGNOR-121572

Q8WTR2

P45983

1

dephosphorylation

down-regulates

0.421

Skrp1 was highly specific for c-jun n-terminal kinase (jnk) in vitro and effectively suppressed the jnk activation in response to tumor necrosis factor alpha or thapsigargin skrp1 does not bind directly to its target jnk, but co-precipitation of skrp1 with the mapk kinase mkk7, a jnk activator, was found in vitro and in vivo.

SIGNOR-117260

Q12923

O00506

1

dephosphorylation

down-regulates activity

0.421

To investigate dephosphorylation of CCM3 by FAP-1, phosphorylated GST-CCM3 was incubated with cdFAP-1, and reactions were analyzed by autoradiography. Again, GST-STK25 phosphorylated GST-CCM3 and possessed autophosphorylation activity. cdFAP-1 of 0.005 U were sufficient to dephosphorylate GST-CCM3 as well as the kinase GST-STK25.|More recently, the Golgi matrix protein GM130 was shown to function as a scaffold protein for STK25 and to activate STK25 through stimulation of autophosphorylation.

SIGNOR-248711

P12931

Q8NEB9

1

phosphorylation

up-regulates activity

0.42

Given that VPS34 is activated by Src mediated tyrosine phosphorylation, we next determined if VPS34 was tyrosine phosphorylated following insulin treatment.|These data indicate that VPS34 is an effector of insulin-mediated signal transduction and that Src phosphorylation of VPS34 is required for this function.

SIGNOR-278456

P17612

P54646

1

phosphorylation

down-regulates

0.42

Pka associates with and phosphorylates ampk?1 At ser-173 to impede threonine thr-172 phosphorylation and thus activation of ampk1 by lkb1 in response to lipolytic signals

SIGNOR-161860

P12931

O75553

1

phosphorylation

up-regulates activity

0.42

Dab1 is rapidly phosphorylated when neurons isolated from embryonic brains are stimulated with Reelin, and several tyrosines have been implicated in this response. Mice with phenylalanine substitutions of all five tyrosines (Tyr(185), Tyr(198), Tyr(200), Tyr(220), and Tyr(232)) exhibit a reeler phenotype, implying that tyrosine phosphorylation is critical for Dab1 function. Here we report that, although Src can phosphorylate all five tyrosines in vitro, Tyr(198) and Tyr(220) represent the major sites of Reelin-induced Dab1 phosphorylation in embryonic neurons.

SIGNOR-247080

P31751

Q6ZWJ1

1

phosphorylation

down-regulates activity

0.42

Akt2 phosphorylates Synip to regulate docking and fusion of GLUT4-containing vesicles. These data demonstrate that insulin activation of Akt2 specifically regulates the docking/fusion step of GLUT4-containing vesicles at the plasma membrane through the regulation of Synip phosphorylation and Synip-Syntaxin4 interaction.Thus, our data demonstrate that insulin-stimulated Akt2-dependent phosphorylation of Synip on serine residue 99 results in reduced binding interactions between Synip and Syntaxin4.

SIGNOR-262635