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O00273
P42574
0
cleavage
up-regulates activity
0.755
DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis. We have identified and purified from HeLa cytosol a protein that induces DNA fragmentation in coincubated nuclei after it is activated by caspase-3.
SIGNOR-47416
Q676U5
Q9HC29
0
binding
up-regulates activity
0.755
By a mechanism independent of the adaptor RIP2 and transcription factor NF-kappaB, Nod1 and Nod2 recruited the autophagy protein ATG16L1 to the plasma membrane at the bacterial entry site. Our results link bacterial sensing by Nod proteins to the induction of autophagy and provide a functional link between Nod2 and ATG16L1, which are encoded by two of the most important genes associated with Crohn's disease.
SIGNOR-252405
O94986
Q96SN8
0
relocalization
up-regulates activity
0.755
Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome.
SIGNOR-271721
P10747
P06239
0
phosphorylation
up-regulates
0.754
We demonstrate that emt can phosphorylate all four tyrosines of the cd28 tail, in contrast to lck, which phosphorylates only tyrosine 173. Together with evidence that in vivo, tyrosines other than tyrosine 173 become phosphorylated following cd28 stimulation, this finding suggests that, like lck, one function of emt during cd28 signaling is phosphorylation of the receptor
SIGNOR-45524
P54760
P98172
0
binding
up-regulates
0.754
Receptors of the epha group preferentially interact with glycosylphosphatidylinositol (gpi)-linked ligands (of the ephrin-a subclass, which comprises five ligands), while receptors of the ephb group preferentially interact with transmembrane ligands (of the ephrin-b subclass, which comprises three ligands) (table 1). In either case, binding of a ligand results in eph receptor autophosphorylation on tyrosine residues and activation of the kinase activity of the eph receptor
SIGNOR-52580
P61586
P10911
0
guanine nucleotide exchange factor
up-regulates activity
0.754
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-260556
P24385
P03372
0
transcriptional regulation
up-regulates quantity by expression
0.754
Ikkalpha in conjunction with eralpha and aib1/src-3, is important in activating the transcription of estrogen-responsive genes, including cyclin d1.
SIGNOR-135053
P37173
P61812
0
binding
up-regulates
0.754
We show that tbetarii-b, an alternatively spliced variant of the tgf-beta type ii receptor, is a tgf-beta2 binding receptor, which mediates signalling via the smad pathway in the absence of any tgf-beta type iii receptor
SIGNOR-104795
O43395
Q9UMS4
0
polyubiquitination
up-regulates activity
0.754
Here, we report that the spliceosomal Prp19 complex modifies Prp3, a component of the U4 snRNP, with nonproteolytic K63-linked ubiquitin chains. The K63-linked chains increase the affinity of Prp3 for the U5 snRNP component Prp8, thereby allowing for the stabilization of the U4/U6.U5 snRNP. 
SIGNOR-271966
O15350
P00519
0
phosphorylation
up-regulates
0.754
C-abl phosphorylates p73 on a tyrosine residue at position 99 both in vitro and in cells that have been exposed to ionizing radiation. Our results show that c-abl stimulates p73-mediated transactivation and apoptosis.
SIGNOR-68931
P78352
Q8N0W4
0
relocalization
up-regulates activity
0.754
Like NRXNs, NLGNs bind to intracellular PDZ-domain proteins, but in contrast to NRXNs, NLGNs bind to class I PDZ domains such as those contained in PSD95, a postsynaptic MAGUK protein65. PSD95 and its homologues are centrally involved in recruiting glutamate receptors at postsynaptic sites66. Similarly to CASK, PSD95 binds to intracellular adaptor proteins, and especially to GKAP (a protein that binds to the guanylate-kinase domain of PSD95), which, in turn, binds to SHANK proteins (Fig. 1b). A possible role of these interactions is to recruit postsynaptic adaptor proteins to the site of synaptic junctions.
SIGNOR-264192
P31749
P78527
0
phosphorylation
up-regulates activity
0.754
DNA-PK phosphorylates HM Ser473 of PKB. However, we also noted similar patterns in T loop Thr308 phosphorylation after _-IR []his function is apparently restricted to the PKBalpha isoform
SIGNOR-252431
P20042
Q9UI10
0
guanine nucleotide exchange factor
up-regulates activity
0.754
EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity.
SIGNOR-269132
P56159
P07949
0
binding
up-regulates
0.754
Gdnfr-alpha-ligand complex, together with the tyrosine kinase receptor (cret) forms a functional receptor that activates downstream signal transduction pathways
SIGNOR-77587
P30307
P24941
0
phosphorylation
up-regulates
0.754
The cyclin e/cdk2 complex phosphorylates cdc25c on ser(214), leading to its premature activation, which coincides with higher cyclin b/cdk1 and polo-like kinase 1 (plk1) activities in an s-phase-enriched population that result in faster mitotic entry.
SIGNOR-165872
Q8N5S9
P0DP23
0
binding
up-regulates
0.754
The binding of Ca2+/CaM to CaM-KK is absolutely required for its activation and efficient phosphorylation of target protein kinases
SIGNOR-232178
P36507
P10398
0
phosphorylation
up-regulates
0.754
Active raf phosphorylates mek.
SIGNOR-175142
P21802
P10767
0
binding
up-regulates
0.753
The nine known fgf ligands and the four signaling fgf receptors (and their alternatively spliced variants) are expressed in specific spatial and temporal patterns. The activity of this signaling pathway is regulated by ligand binding specificity, heparan sulfate proteoglycans, and the differential signaling capacity of individual fgf receptors.
SIGNOR-42380
Q8NB16
Q9Y572
0
phosphorylation
up-regulates activity
0.753
MLKL comprises a four-helical bundle tethered to the pseudokinase domain, which contains an unusual pseudoactive site. Although the pseudokinase domain binds ATP, it is catalytically inactive and its essential nonenzymatic role in necroptotic signaling is induced by receptor-interacting serine-threonine kinase 3 (RIPK3)-mediated phosphorylation.[...]S345, S347, and T349 in the MLKL activation loop were phosphorylated by RIPK3 in in vitro kinase assays
SIGNOR-266427
P0DMV8
Q9UL15
0
binding
down-regulates activity
0.753
Here, we show that BAG5, a BAG domain-containing family member, interacts with both Hsp70 and parkin with deleterious functional consequences. Through these interactions, BAG5 inhibits Hsp70 chaperone activity and parkin E3 ubiquitin ligase activity; Thus, BAG5 interacts with Hsp70 in vitro and in vivo, and substitution of select residues within the BAG domains is sufficient to abolish this interaction.
SIGNOR-261196
Q14332
P56704
0
binding
up-regulates
0.753
It was also shown that wnt5a inhibits the beta-catenin pathway by competing with wnt3a for binding to fz2, and that the impairment of clathrin-mediated internalization does not affect this wnt5a inhibitory action.
SIGNOR-189117
Q07812
P04637
0
binding
up-regulates
0.753
P53 also accumulates in the cytoplasm where it directly activates bax to promote mitochondrial outer membrane permeabilization.
SIGNOR-140242
Q06609
Q86YC2
0
binding
up-regulates
0.753
We propose that both palb2 chromatin association and its oligomerization serve to secure the brca2 x rad51 repair machinery at the sites of dna damage.
SIGNOR-185656
Q7Z434
Q86UT6
0
binding
down-regulates activity
0.753
Here we describe human NLRX1, a highly conserved nucleotide-binding domain (NBD)- and leucine-rich-repeat (LRR)-containing family member (known as NLR) that localizes to the mitochondrial outer membrane and interacts with MAVS. Expression of NLRX1 results in the potent inhibition of RLH- and MAVS-mediated interferon-beta promoter activity and in the disruption of virus-induced RLH-MAVS interactions. Co-immunoprecipitation studies demonstrate that HA–NLRX1 interacts with MAVS but not with other known mitochondrial outer membrane proteins (BCL2 and BCL2L1), indicating specificity of the NLRX1–MAVS interaction. Finally, endogenous NLRX1 associates strongly with endogenous MAVS after immunoprecipitation with two different MAVS antibodies
SIGNOR-260357
P54840
Q9UQK1
0
binding
up-regulates
0.753
In the liver, PTG and PPP1R3B(GL)are expressed at roughly equivalent levels [55], and they jointly promote hepatic glycogen mobilization and storage. PTG overexpression significantly increased glycogen content, mainly due to its ability to promote the redistribution of PP1 and glycogen synthase to glycogen granules, significantly increasing GS activity and glycogen synthesis (Figure 2)
SIGNOR-271731
P35222
Q9UI47
0
relocalization
up-regulates quantity
0.753
Overexpression of CTNNA3 in a CTNNA1 negative colon carcinoma cell line resulted in the reassembly of the adherens and tight junctions through the recruitment of CTNNA3 interacting partners such as E-cadherin, β-catenin, plakoglobin, and ZO-14
SIGNOR-265493
P20042
P78344
0
binding
up-regulates activity
0.753
Unlike eIF4GI/II, DAP5 binds eIF2β, a subunit of the eIF2 complex that delivers methionyl-tRNA to ribosomes.
SIGNOR-266385
P16885
P43405
0
phosphorylation
up-regulates activity
0.753
Syk in turn phosphorylates and activates the B cell linker protein (BLNK), phosphoinositide 3-kinase (PI3K) and phospholipase C\u03b32 (PLC\u03b32).|Syk in turn phosphorylates and activates the B cell linker protein (BLNK), phosphoinositide 3-kinase (PI3K) and phospholipase Cgamma2 (PLCgamma2).
SIGNOR-278995
Q9UKT4
P06493
0
phosphorylation
down-regulates quantity by destabilization
0.753
We find that both Emi1 phosphorylation by cyclin and Cdc2 and phosphorylation on a consensus site (DSGxxS) direct recruitment of betaTrCP and subsequent Emi1 ubiquitination and destruction.
SIGNOR-279143
O14786
Q13214
0
binding
up-regulates activity
0.753
Further examination of the composition of the functional Sema3B receptor revealed that, unlike Sema3A, which signals exclusively using the NP1 receptor, Sema3B utilizes both NP1 and NP2 for signal transduction.
SIGNOR-261814
Q07820
Q9BXH1
0
binding
down-regulates
0.752
Only bimbh3 and bbc3 had comparable strong affinities for all the prosurvival proteins. The members that promote cell survival, including mammalian bcl-2, bcl-xl,bcl-w, mcl-1, and a1.
SIGNOR-133817
P45983
P45985
0
phosphorylation
up-regulates activity
0.752
Stress-activated protein kinase 1 (SAPK1), also called c-Jun N-terminal kinase (JNK), becomes activated in vivo in response to pro-inflammatory cytokines or cellular stresses. Its full activation requires the phosphorylation of a threonine and a tyrosine residue in a Thr-Pro-Tyr motif, which can be catalysed by the protein kinases mitogen-activated protein kinase kinase (MKK)4 and MKK7. Here we report that MKK4 shows a striking preference for the tyrosine residue (Tyr-185), and MKK7 a striking preference for the threonine residue (Thr-183) in three SAPK1/JNK1 isoforms tested (JNK1 alpha 1, JNK2 alpha 2 and JNK3 alpha 1).
SIGNOR-251419
P27361
Q02750
0
phosphorylation
up-regulates
0.752
Mek1 as indicated by extensive phosphorylation of erk1 and erk2 during the initial 2 h of adipogenesis.
SIGNOR-210176
P25025
P42830
0
binding
up-regulates activity
0.752
CXCL5 is another ELR+ CXC chemokine and, thus, also potently attracts neutrophils. Just like CXCL1, CXCL5 also signals through CXCR2, explaining why, often, CXCL5 and CXCL1 are seen to function in parallel in PDAC. CXCL5 was increased in human pancreatic tissue compared to the normal pancreas, and the knockdown of CXCL5 in pancreatic cancer cell lines reduced the proliferation and migration ability of cells
SIGNOR-277730
Q13469
P45983
0
phosphorylation
down-regulates
0.752
Jnks directly phosphorylate nuclear factor of activated t-cell (nfat) transcription factors, thus antagonizing the effects of calcium-regulated signaling through the protein phosphatase calcineurin jnk directly regulated nuclear factor of activated t-cell (nfat) activation in culture and in transgenic mice containing an nfat-dependent luciferase reporter.
SIGNOR-118217
P15498
O43561
0
binding
up-regulates activity
0.752
By substituting these tyrosine residues in LAT with phenylalanine and by utilizing phosphorylated peptides derived from these sites, we mapped the tyrosine residues in LAT required for the direct interaction and activation of Vav, p85/p110alpha and phospholipase Cgamma1 (PLCgamma1). Our results indicate that Tyr(226) and Tyr(191) are required for Vav binding, whereas Tyr(171) and Tyr(132) are necessary for association and activation of phosphoinositide 3-kinase activity and PLCgamma1 respectively.
SIGNOR-246045
O14641
Q9ULV1
0
binding
up-regulates activity
0.751
Through study of FZD4 and its associated ligand Norrin, we report that a minimum of three residues distal to the KTXXXW motif in the C-terminal tail of Frizzled-4 are essential for DVL recruitment and robust Lef/Tcf-dependent transcriptional activation in response to Norrin.
SIGNOR-258958
Q01113
P15248
0
binding
up-regulates
0.751
Interleukin 9 (il-9) exerts its pleiotropic effects through the il-9 receptor (il-9r) complex, which consists of the il-9r alpha-chain, which determines the cytokine specificity, and the il-2 receptor gamma-chain
SIGNOR-73601
Q08209
P0DP23
0
binding
up-regulates
0.751
Calcium-bound calmodulin associates with calcineurin (cn), releasing the phosphatase from the repressive effects on an autoinhibitory domain.
SIGNOR-114098
Q676U5
Q9H082
0
binding
up-regulates
0.751
Olgi-resident small gtpase rab33b interacts with atg16l and modulates autophagosome formation.
SIGNOR-178542
P16615
P26678
0
binding
down-regulates activity
0.751
Heart failure can be traced, in part, to alterations in the activity of the sarcoplasmic reticulum Ca2+ pump that are induced by its interactions with phospholamban, a reversible inhibitor.
SIGNOR-252031
P40189
P08887
0
binding
up-regulates
0.751
Part of the receptor for interleukin 6. Binds to il6 with low affinity, but does not transduce a signal. Signal activation necessitate an association with il6st. Activation may lead to the regulation of the immune response, acute-phase reactions and hematopoiesis.
SIGNOR-105504
Q9UNE0
Q92838
0
binding
up-regulates
0.751
Ultimately, in mammals, eda-a1 and eda-a2 trimers each bind a different receptor, edar and xedar, respectively, through their trimerized tnf domain.
SIGNOR-161109
Q9Y5S8
Q86UR1
0
binding
up-regulates activity
0.751
Tks4 and Tks5 bind NoxA1 through their SH3 domains in a Rac-independent manner|NoxO1 is required for full Nox1 and Nox3 oxidase activity at least partially because of its role in the plasma membrane recruitment of the NoxA1 activator protein|Tks4 and Tks5 support Nox1- and Nox3-dependent ROS generation
SIGNOR-264710
O43524
P31751
0
phosphorylation
down-regulates activity
0.751
Akt-dependent phosphorylation of foxo3a (thr32, ser253, and ser315 for human foxo3) enhances foxo3a/14-3-3 Interaction and promotes foxo3a nuclear export to the cytoplasm, resulting in the repression of foxo3a transcriptional function akt phosphorylates members of the foxo factors (forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localisation. In particular, akt phosphorylates foxo1 on thr24, ser256 and ser319. Foxo 3alfa and foxo4 are phosphorylated on equivalent sites.
SIGNOR-236671
Q15398
O14965
0
phosphorylation
up-regulates quantity by stabilization
0.751
Phosphorylation and stabilization of HURP by Aurora-A. Four phosphorylated residues were identified, namely, HURP-S627, -S725, -S757, and -S830, with 65% amino acid sequence coverage. we propose here that Aurora-A may phosphorylate HURP and this probably attenuates the negative impact of cdk1 phosphorylation and by inhibiting subsequent proteasome activity and this will generate a longer HURP half-life.
SIGNOR-262651
Q15382
Q12983
0
binding
down-regulates
0.751
Bnip3, a hypoxia-inducible bcl-2 homology 3 domain-containing protein, directly binds rheb and inhibits the mtor pathway. Bnip3 decreases rheb gtp levels in a manner depending on the binding to rheb.
SIGNOR-158274
P60953
O15068
0
guanine nucleotide exchange factor
up-regulates activity
0.751
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-260560
P48740
P11226
0
binding
up-regulates activity
0.751
The results (Fig. 3A) show that the anti-MBL antibody, in addition to binding MBL captures both MASP-1 and MASP-2|Our results emphasize the similarity between complement activation through the MBL, or 'MBLectin' pathway of the innate immune system and the classical pathway of complement activation (Fig. 5).
SIGNOR-263414
Q9UKG1
Q96A54
0
binding
up-regulates
0.751
Appl1 interacts with adiponectin receptors in mammalian cells and the interaction is stimulated by adiponectin.
SIGNOR-146212
P40189
P13725
0
binding
up-regulates
0.751
Stimulation of cells with the interleukin-6 family of cytokines triggers homo- or hetero-dimerization of gp130. The dimerization of gp130 leads to activation of associated cytoplasmic tyrosine kinases and subsequent modification of transcription factors. Some of these biological activities of il-6 are also often exerted by other cytokines, i.e. Il-11, lif, osm, cntf, and ct-2.
SIGNOR-48114
P22223
O60716
0
binding
up-regulates quantity by stabilization
0.751
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-252124
Q13671
P00519
0
phosphorylation
up-regulates
0.751
We also report that the amino-terminal domain of rin1 contains sequences that can mediate interactions with the abl tyrosine kinase and that rin1 is itself tyrosine phosphorylated by c-abl.
SIGNOR-48142
P20042
P49770
0
guanine nucleotide exchange factor
up-regulates activity
0.751
EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity.
SIGNOR-269130
P06239
Q9Y2R2
0
dephosphorylation
down-regulates activity
0.751
In vitro experiments with purified recombinant proteins demonstrated that PTPN22-D195A/C227S interacted directly with activated Lck, Zap70, and TCRzeta, confirming the initial substrate trap results. Native PTPN22 dephosphorylated Lck and Zap70 at their activating tyrosine residues Tyr-394 and Tyr-493, respectively, but not at the regulatory tyrosines Tyr-505 (Lck) or Tyr-319 (Zap70). Native PTPN22 also dephosphorylated TCRzeta in vitro and in cells, and its substrate trap variant co-immunoprecipitated with TCRzeta when both were coexpressed in 293T cells, establishing TCRzeta as a direct substrate of PTPN22.
SIGNOR-248836
P40763
P28482
0
phosphorylation
down-regulates activity
0.75
ERK2 phosphorylates Stat3 on three serine-containing peptides and decreases its tyrosine phosphorylation induced by EGF treatment.|Here, we report that ERK2 activated by its upstream kinase, MEK1, represses Stat3 transcriptional activity induced by Src or Jak-2.
SIGNOR-279635
P61586
P52735
0
guanine nucleotide exchange factor
up-regulates activity
0.75
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-260582
Q08050
P24941
0
phosphorylation
up-regulates activity
0.75
We demonstrated that FoxM1B transcriptional activity requires binding of either S-phase or M-phase Cdk-cyclin complexes to mediate efficient Cdk phosphorylation of the FoxM1B Thr 596 residue, which is essential for recruitment of p300/CBP coactivator proteins.
SIGNOR-250731
P63000
Q13009
0
binding
up-regulates
0.75
Lpa-induced rac activation requires tiam1
SIGNOR-94691
P29322
O43921
0
binding
up-regulates
0.75
The activation of eph receptors by their ligands, which are membrane-anchored molecules, involves a cell-cell recognition event that often causes cell repulsion. Therefore, eph receptors mediate signals that can override cell adhesion.
SIGNOR-52269
P61088
O76064
0
binding
up-regulates
0.75
The rnf8 ring domain signals ubc13 to sites of damage, which is sufficient for dna damage signal transduction.
SIGNOR-179823
Q15303
Q99075
0
binding
up-regulates
0.75
It was concluded that her4 is a newly described receptor for hb-egf and that hb-egf can activate two egf receptor subtypes, her1 and her4, but with different biological response.
SIGNOR-67009
P29322
P52797
0
binding
up-regulates
0.75
Receptors of the epha group preferentially interact with glycosylphosphatidylinositol (gpi)-linked ligands (of the ephrin-a subclass, which comprises five ligands), while receptors of the ephb group preferentially interact with transmembrane ligands (of the ephrin-b subclass, which comprises three ligands) (table 1). In either case, binding of a ligand results in eph receptor autophosphorylation on tyrosine residues and activation of the kinase activity of the eph receptor
SIGNOR-52387
Q13177
P63000
0
binding
up-regulates activity
0.75
A new brain serine/threonine protein kinase may be a target for the p21ras-related proteins Cdc42 and Rac1. The kinase sequence is related to that of the yeast protein STE20, implicated in pheromone-response pathways.
SIGNOR-248250
P36507
P15056
0
phosphorylation
up-regulates
0.75
We show that, consequently, b-raf interacts with mek-1 and mek-2 with a better affinity than does c-raf-1, thus strengthening the notion that b-raf is a stronger mek activator than c-raf-l.
SIGNOR-42664
O60841
P55010
0
relocalization
up-regulates activity
0.75
eIF5B promotes ribosomal subunit joining, with the help of eIF1A. Upon subunit joining, eIF5B hydrolyzes GTP and is released together with eIF1A. We found that human eIF5 interacts with eIF5B and may help recruit eIF5B to the PIC.
SIGNOR-269122
P61586
P15498
0
guanine nucleotide exchange factor
up-regulates activity
0.75
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-260580
P42229
P12931
0
phosphorylation
up-regulates
0.75
Src can thus directly tyrosine-phosphorylate the activation site of stat5 (tyr 694 in stat5a), and src may contribute to epo-induced signal transduction via stat5.
SIGNOR-111078
P84022
P05412
0
binding
down-regulates activity
0.75
These results indicate that interaction between Smad3 and c-Jun may repress Smad3 transcriptional activity.
SIGNOR-256284
Q9H8V3
P53350
0
phosphorylation
up-regulates activity
0.75
Phosphorylation of Ect2 by Plk1 during anaphase might alleviate this intramolecular inhibition by dissociating the Ect2 amino from the carboxyl terminus.|Together with the presence of a prominent microtubule array at the midzone, these data suggest that Plk1 is not essential for the formation of the central spindle at anaphase.The specific failure of Ect2 to localize to the midzone raised the interesting possibility that Plk1 might trigger the initiation of cytokinesis by promoting the interaction of Ect2 with centralspindlin and, thereby, Ect2 activation and recruitment to the central spindle.
SIGNOR-279553
Q9UF33
O43921
0
binding
up-regulates
0.75
Ephrin-a ligands (named ephrin-a1_ephrin-a5) are anchored in the plasma membrane through a gpi-linkage, and each can bind any of the epha subclass of receptors (epha1_epha8)
SIGNOR-65419
Q9UK05
P17813
0
binding
up-regulates activity
0.749
Soluble endoglin specifically binds bone morphogenetic proteins 9 and 10 via its orphan domain, inhibits blood vessel formation, and suppresses tumor growth. We found that mouse and human endoglin ECD-Fc bound directly, specifically, and with high affinity to bone morphogenetic proteins 9 and 10 (BMP9 and BMP10) in surface plasmon resonance (Biacore) and cell-based assays.
SIGNOR-276656
P10415
P04637
0
binding
down-regulates activity
0.749
Mechanistic insights into the mitochondrial function of wtp53 came when it was realized that mitochondrially translocated p53 interacts directly with members of the Bcl-2 family, which are central in governing the induction of mitochondrial outer membrane permeabilization. In response to stress, wtp53 interacts with and neutralizes the anti-apoptotic members Bcl-xL and Bcl-2. This interaction stimulates MOMP and subsequent apoptosis
SIGNOR-99712
P31749
Q15119
0
phosphorylation
up-regulates activity
0.749
PIP3 recruits PDK1 and AKT to the plasma membrane, where PDK1 phosphorylates AKT on Thr308 in the activation loop of the kinase domain. The phosphorylation of AKT on Ser473 by PDK2 acts as a €œgain control€ for AKT and regulates its degree of activation. The sirolimus-insensitive mTORC2 complex exhibits PDK2 activity
SIGNOR-249630
O43561
P06241
0
phosphorylation
up-regulates
0.749
Both lck and syk, phosphorylate the itam-like motifs on lat at y171y191, which is essential for induction of the interaction of lat with downstream signaling molecules such as grb2, plc-gamma1 and c-cbl, and for activation of mapk-erk.
SIGNOR-149174
O43683
Q96GD4
0
phosphorylation
up-regulates activity
0.749
Although our analysis identified only one of the 15 sites implicated in Bub1-Mad1 interaction, it suggests that following its rapamycin-induced dimerization, Ipl1 phosphorylates Bub1, and potentially Mad1, to drive eSAC signaling.
SIGNOR-279010
Q9UQK1
O95278
0
dephosphorylation
up-regulates quantity by stabilization
0.749
We have recently described that the activity of R5/PTG is down-regulated by the laforin-malin complex, composed of a dual specificity phosphatase (laforin) and an E3-ubiquitin ligase (malin). We now demonstrate that phosphorylation of R5/PTG at Ser-8 by AMPK accelerates its laforin/malin-dependent ubiquitination and subsequent proteasomal degradation, which results in a decrease of its glycogenic activity. 
SIGNOR-276239
Q9ULH4
P78352
0
binding
up-regulates activity
0.749
SALMs 1-3 contain a C-terminal PDZ-binding motif, which interacts with PSD-95, an abundant postsynaptic scaffolding protein, whereas SALM4 and SALM5 lack PDZ binding. Interactions between SALMs 1–3 and PSD-95 family proteinscould serve a number of functions. SALM1 and SALM2, which lack the ability to interact with a presynaptic ligand and thus cannot be directly targeted to sites of early synaptic adhesion, may require PSD-95 binding for their localization to early synapses.
SIGNOR-264094
Q00610
Q13492
0
binding
up-regulates
0.749
Calm interacts with the clathrin heavy chain through its c-terminal third and with phophoinositides through its ap180 n-terminal homology (anth) domain, promoting assembly of clathrin triskelia into clathrin cagesin vitro
SIGNOR-144683
P01106
P24941
0
phosphorylation
up-regulates quantity by stabilization
0.749
Cdk2 phosphorylates c-Myc at Ser62 to suppress its ubiquitination modification/degradation, resulting in enhanced stability of c-Myc [ xref ].
SIGNOR-279808
P16410
P06239
0
phosphorylation
up-regulates quantity by stabilization
0.749
Lck and Fyn, but not ZAP70, induce tyrosine phosphorylation of CTLA-4 in the cell line HEK293. Phosphorylation of CTLA-4 occurs on both Y201 and Y218. Phosphorylation of Y201 correlated with accumulation of CTLA-4 on the cell surface.
SIGNOR-251370
P31749
O15530
0
phosphorylation
up-regulates
0.748
We have partially purified a kinase from brain extract that phosphorylates Ser473 of PKBalpha in a PtdIns(3,4,5)P3-dependent manner and that is immunoprecipitated with PDK1 antibodies.
SIGNOR-67367
Q15796
P27361
0
phosphorylation
down-regulates
0.748
These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3
SIGNOR-66778
Q16611
Q07817
0
binding
down-regulates
0.748
Bax is held in check by mcl1, bcl-2, and either bcl2l1 or bcl2l2, or by all four. They bind a primed conformer of bak or bax
SIGNOR-152983
P49427
Q9UBF6
0
polyubiquitination
down-regulates activity
0.748
SAG was found to be the second family member of Rbx (RING box protein) or ROC (Regulator of cullins) or Hrt that is a component of SCF E3 ubiquitin ligase. Indeed, like ROC1/Rbx1/Hrt1, SAG binds to Cul1 and SAG-Cul1 complex has ubiquitin ligase activity to promote poly-ubiquitination of E2/Cdc34. 
SIGNOR-271443
Q07666
Q13882
0
phosphorylation
up-regulates
0.748
Sik/brk is the first identified tyrosine kinase that can phosphorylate sam68 and regulate its activity within the nucleus, where it resides during most of the cell cycle
SIGNOR-80020
Q15303
P56975
0
binding
up-regulates
0.748
The neuregulins (also called heregulins and neu differentiation factors) nrg-1 and nrg-2 bind erbb-3 and erbb-4;and nrg-3 and nrg-4 bind erbb-4.
SIGNOR-26251
Q06609
O43542
0
binding
up-regulates quantity by stabilization
0.748
XRCC3 activation is essential for the recruitment of RAD51 to the sites of DNA lesions. It is likely that BRCA2 may directly participate in RAD51 recruitment and XRCC3 may stabilize the RAD51 filament which is in part mediated by phosphorylation.
SIGNOR-262667
Q9NRM6
Q9UHF5
0
binding
up-regulates
0.748
Here we report on the discovery of a novel il-17 homolog (il-17b), together with the identification of a novel cell surface receptor that specifically binds to it. We detail the molecular cloning, tissue distribution, and expression of both il-17b and il-17br, describe thein vivo activity of il-17b, and demonstrate binding to il-17br.
SIGNOR-76544
P40763
P42345
0
phosphorylation
up-regulates
0.748
Serine phosphorylation and maximal activation of stat3 during cntf signaling is mediated by the rapamycin target mtor. / a stat3 peptide was efficiently phosphorylated on ser727 in a cntf-dependent manner by mtor
SIGNOR-146915
P31751
P67775
0
dephosphorylation
down-regulates activity
0.748
Overexpression of BTBD10 increased phosphorylation levels of Akts at both Thr(308) and Ser(473) while the reduction of the endogenous BTBD10 level resulted in a decrease in the phosphorylation levels of Akts. In vitro analysis indicated that BTBD10 bound to protein phosphatase 2A (PP2A) and inhibited dephosphorylation of Akts by PP2A.
SIGNOR-248632
Q13546
Q13489
0
polyubiquitination
up-regulates activity
0.747
CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation.
SIGNOR-272713
P52272
O43660
0
binding
up-regulates activity
0.747
hnRNP-M interacts directly with CDC5L and PLRG1 in vivo. we investigated whether the function of hnRNP-M in alternative splicing was affected by the central region mapped as essential for binding to the CDC5L/PLRG1 proteins. We conclude that loss of the CDC5L/PLRG1 interaction domain in hnRNP-M correlates with a loss of ability to modulate alternative splice site selection in this assay.
SIGNOR-239444
P00533
P35070
0
binding
up-regulates
0.747
Betacellulin is synthesized primarily as a transmembrane precursor, which is then processed to mature molecule by proteolytic events;ten growth factors and their erbb specificities are depicted: egf, amphiregulin((ar), and tgfalfa bind erbb-1, betacellulin, heparin binding egf-like growth factor, and epiregulin bing both erbb-1 and erbb-4.
SIGNOR-121953
Q01973
P41221
0
binding
up-regulates
0.747
Ror1 and ror2 bind wnt5a.
SIGNOR-196133
P22681
Q96B97
0
binding
up-regulates
0.747
The cin85 sh3 domains interact with c-cbl, an e3 ubiquitin ligase, via an unconventional pxxxpr ligand sequence, with the highest affinity displayed by the sh3-b domain. Interaction with cin85 recruits c-cbl to the amap1 complex where its ubiquitination activity is necessary for cancer cells to develop an invasive phenotype and to degrade the matrix.
SIGNOR-203139
Q9GZZ7
O60542
0
binding
up-regulates
0.747
Glial cell line-derived neurotrophic factor (gdnf) family ligands signal through receptor complex consisting of a glycosylphosphatidylinositol-linked gdnf family receptor (gfr) alpha subunit and the transmembrane receptor tyrosine kinase ret.
SIGNOR-85162
P19838
O15111
0
phosphorylation
down-regulates quantity by destabilization
0.747
All residues of p105 phosphorylated by ikka are c-terminal; the major phosphorylation region contains three serines (ser923; ser927;ser932) and two threonines (thr927 and thr391).
SIGNOR-70449
P04637
P45984
0
phosphorylation
up-regulates
0.747
These findings strongly suggest that jnks are the major direct signaling mediators of uvb-induced p53 phosphorylation at serine 20. furthermore, phosphorylation of p53 at serine 20 by uvb-activated jnks and uvb-induced p53-dependent transcriptional activity were suppressed in jnk1 or jnk2 knockout (jnk1(-/-) or jnk2(-/-)) cells.
SIGNOR-115835
Q13315
Q13535
0
phosphorylation
up-regulates activity
0.747
Atr-dependent phosphorylation and activation of atm in response to uv treatment or replication fork stalling. Here, we show that atm phosphorylation at ser1981, a characterised autophosphorylation site, is atr-dependent and atm-independent following replication fork stalling or uv treatment
SIGNOR-150870