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mechanism
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14
Q9GZQ6
O15130
0
binding
up-regulates
0.747
Npff specifically bound to npff1 (k(d) = 1.13 nm) and npff2 (k(d) = 0.37 nm), and both receptors were activated by npff in a variety of heterologous expression systems
SIGNOR-82916
P46527
O43524
0
transcriptional regulation
up-regulates quantity
0.747
AFX transcriptionally activates p27kip1, resulting in increased protein levels.
SIGNOR-238610
O15169
P49674
0
phosphorylation
up-regulates
0.747
We conclude that a major role of axin in the wnt is to provide the kinase activity that initiates the betBeta-catenin phosphorylation cascade at s45. This process is mediated by cki, the alfa, delta, or ? Isoform, all detected in association with axin by lc/ms.
SIGNOR-87444
P16220
Q15418
0
phosphorylation
up-regulates activity
0.747
The rsks phosphorylate the trascription factor creb at serine 133 to promote cell survival.
SIGNOR-72117
P13639
Q9H2P9
0
methylation
down-regulates activity
0.747
Analysis of EF2 in the mutant cells revealed a novel form of diphthamide with an additional methyl group that prevented ADP-ribosylation and inactivation of EF2. The abnormal methylation appeared to be catalyzed by DPH5.
SIGNOR-261146
Q8TDY2
Q8IYT8
0
phosphorylation
up-regulates activity
0.747
When mTOR is inhibited, ULK1 and ULK2 activate and phosphorylate ATG13 and FIP200.
SIGNOR-280159
P84022
P28482
0
phosphorylation
down-regulates activity
0.746
Phosphorylation of the linker region of smads mediated by erk2, gsk3?, And cdk2/4 negatively regulates smad activity by preventing their relocation to the nucleus, by inhibiting their interactions with coactivators, or by accelerating their degradation;in contrast, erk2 phosphorylated all four smad1 residues almost evenly, while showing a preference for s204 over s208 and s213 in smad3
SIGNOR-161613
P35222
Q9UKB1
0
binding
down-regulates
0.746
We conclude that beta-trcp is a component of an e3 ubiquitin ligase that is responsible for the targeted degradation of phosphorylated beta-catenin. we found that the binding of beta-trcp to beta-catenin was direct.
SIGNOR-65429
O43583
Q9ULC4
0
binding
up-regulates activity
0.746
The MCT-1 protein modifies mRNA translational profiles through its interaction with DENR/DRP, a protein containing an SUI1 domain involved in recognition of the translation initiation codon. 
SIGNOR-269674
P23769
Q8IX07
0
transcriptional regulation
down-regulates quantity by repression
0.746
GATA-2 induces the expression of GATA-1, which first activates its cofactor FOG-1, and then downregulates GATA-2 cooperatively with FOG-1.
SIGNOR-256061
P55199
Q96CJ1
0
binding
up-regulates
0.746
The eaf1-related eaf2 protein is also a positive regulator of ell elongation activity
SIGNOR-138540
P52333
P31785
0
binding
up-regulates
0.746
Jak3 is associated with the ?c20,21. Cytokine binding mediates the trans-phosphorylation of receptor associated jak kinases, which in turn phosphorylate tyrosine residues on the receptors themselves. The receptor phosphotyrosines serve as docking sites for sh2 domain proteins including the stat family of transcription factors which are activated by jak-mediated phosphorylation.
SIGNOR-178491
O95487
Q9NR31
0
binding
up-regulates quantity
0.746
Biogenesis of COPII vesicles is initiated by the activation of the small guanosine triphosphate (GTP)-binding protein secretion-associated Ras-related protein 1 (Sar1) at specialized subdomains of the ER, called ER exit sites (ERES) or transitional ER (tER). Membrane-bound Sar1 then recruits the inner COPII coat subcomplex, the Sec23/24 heterodimer.
SIGNOR-265300
P48200
Q9UKA1
0
binding
down-regulates quantity by destabilization
0.746
 We found that a SKP1-CUL1-FBXL5 ubiquitin ligase protein complex associates with and promotes the iron-dependent ubiquitination and degradation of IRP2. The F-box substrate adaptor protein FBXL5 was degraded upon iron and oxygen depletion in a process that required an iron-binding hemerythrin-like domain in its N terminus. 
SIGNOR-271882
P46531
Q9H488
0
binding
up-regulates
0.745
Notch_ is modified in its epidermal growth factor-like domains by the addition of_ fucose_ to serine or threonine residues. O-fucosylation is mediated by protein o-fucosyltransferase 1 and down-regulation of this enzyme by rna interference or mutation of the ofut1 gene in drosophila or by mutation of the pofut1 gene in mouse prevents notch signaling.
SIGNOR-104627
P37231
Q9Y618
0
transcriptional regulation
down-regulates quantity by repression
0.745
In differentiated adipocyte cell lines, SIRT1 inhibits adipogenesis and enhances fat mobilization through lipolysis by suppressing the activity of PPARγ. SIRT1 achieves this by promoting the assembly of a corepressor complex, involving NCoR1 and SMRT, on the promoters of PPARγ target genes to repress their transcription.
SIGNOR-253508
P04150
Q13451
0
binding
down-regulates
0.745
When not associated with glucocorticoids, glucocorticoid receptors are predominantly found in the cytoplasm as part of a multimeric molecular chaperone complex that includes several heat shock proteins (HSPs), such as HSP70 and HSP90, the HSP90_binding protein p23 (also known as PTGES3) and proteins that help to bind HSP90 such as FK506_binding protein 5 (FKBP5).
SIGNOR-251666
P51681
P10147
0
binding
up-regulates activity
0.745
The purpose of this study was to determine whether certain chemokines, which are highly expressed in injured skeletal muscle, are involved in the repair and functional recovery of the muscle after traumatic injury. In wild-type control mice, mRNA transcripts of macrophage inflammatory protein (MIP)-1􏰂, MIP-1􏰃, and monocyte chemoattractant protein (MCP)-1 as well as their major receptors, CCR5 and CCR2, increased after freeze injury and gradu- ally returned to control (uninjured) levels by 14 days.
SIGNOR-251724
Q9UHF4
Q9UHD0
0
binding
up-regulates
0.745
Il-19 signals only through the type i il-20r complex.
SIGNOR-110671
Q14247
Q05397
0
phosphorylation
down-regulates activity
0.745
FAK directly phosphorylates cortactin at Y421 and Y466 and over-expression of cortactin Y421, Y466, and Y482 mutated to phenylalanine (3YF) prevented FAK-enhanced FA turnover and cell motility.|GFP-FAK re-expression in FAK-/- MEFs enhances FA turnover (XREF_FIG) and cortactin knockdown slows FA turnover (XREF_FIG).
SIGNOR-278283
P28482
Q05923
0
dephosphorylation
down-regulates
0.745
Pac1 and mkp-1 previously have been implicated in the in vivo inactivation of erk or of erk and jnk, respectively.
SIGNOR-40915
Q9UM11
P24941
0
phosphorylation
down-regulates activity
0.745
 A nuclear localization signal conserved in various species was identified in CDH1, and it sufficiently targets green fluorescent protein to the nucleus. Interestingly, a CDH1-4D mutant mimicking the hyperphosphorylated form was constitutively found in the cytoplasm. In further support of the notion that phosphorylation inhibits nuclear import, the nuclear localization signal of CDH1 with two phospho-accepting serine/threonine residues changed into aspartates was unable to drive heterologous protein into the nucleus. 
SIGNOR-250732
Q96EB6
Q8N163
0
binding
down-regulates activity
0.745
 Here, we report that, in human cell lines, DNA damage triggered the phosphorylation of DBC1 on Thr454 by ATM (ataxia telangiectasia-mutated) and ATR (ataxia telangiectasia and Rad3-related) kinases. Phosphorylated DBC1 bound to and inhibited SIRT1, resulting in the dissociation of the SIRT1-p53 complex and stimulating p53 acetylation and p53-dependent cell death. 
SIGNOR-267663
Q13485
Q9HCE7
0
ubiquitination
down-regulates activity
0.745
Smurfs, which otherwise cannot directly bind to smad4, mediated poly-ubiquitination of smad4 in the presence of smad6 or smad7. Smad signaling is negatively regulated by inhibitory (i) smads and ubiquitin-mediated processes.
SIGNOR-236096
Q07812
Q07817
0
binding
down-regulates
0.745
The presence of an anti-apoptotic molecule such as bcl-2 or bcl-xl can inhibit the activation of bax following a death signal.
SIGNOR-59141
P36897
P61812
0
binding
up-regulates
0.745
Tgf-? Signaling mediates a wide range of biological activities in development and disease. Tgf-? Ligands signal through heterodimeric type i and type ii receptors (tgf-? Receptor type i [t?RI, also known as alk5 and tgfbr1] and t?RII) that are members of the serine/threonine kinase family.
SIGNOR-196025
P40424
P55347
0
binding
up-regulates activity
0.745
we show that Pbx proteins exist as stable heterodimers with a novel homeodomain protein, Prep1. Here we show that Prep1-Pbx interaction presents novel structural features: it is independent of DNA binding and of the integrity of their respective homeodomains, and requires sequences in the N-terminal portions of both proteins. The Prep1-Pbx protein-protein interaction is essential for DNA-binding activity.
SIGNOR-241212
Q12955
O94856
0
relocalization
up-regulates quantity
0.745
Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains.
SIGNOR-266717
P28482
P36507
0
phosphorylation
up-regulates
0.744
Mapk1 is phosphorylated by map2k1/mek1 and map2k2/mek2 on thr-185 and tyr-187 in response to external stimuli like insulin or ngf. Both phosphorylations are required for activity.
SIGNOR-86709
Q9Y566
Q86YM7
0
binding
up-regulates activity
0.744
It has been shown that Homer, a scaffold protein with a single EVH1 domain that binds to Shank, mGluR1, and other postsynaptic proteins (98) (Figure 3), exists as a tetramer, thus allowing it to cross-link several interacting proteins in the PSD
SIGNOR-264243
Q16539
P52564
0
phosphorylation
up-regulates activity
0.744
These data indicate that mkk6 phosphorylates p38 map kinase on thr-180 and tyr-182, the sites of phosphorylation that activate p38 map kinase
SIGNOR-40427
P53779
P45985
0
phosphorylation
up-regulates
0.744
Two mapkks, sek1 and mkk7, synergistically activate jnk. Sek1 prefers the tyr-185 residue, and mkk7 prefers the thr-183 residue (17, 19).
SIGNOR-137605
P29353
P06239
0
phosphorylation
up-regulates activity
0.744
We show that during TCR signaling, the tyrosines Y239, Y240 and Y317 of Shc are the primary sites of tyrosine phosphorylation. CD4/Lck-dependent tyrosine phosphorylation on Shc was markedly diminished when Y317 was mutated, suggesting a preference of Lck for the Y317 site. tyrosine phosphorylation of Shc may play a key role in T lymphocyte proliferation via interaction of phosphorylated Shc with downstream molecules involved in activation of Ras and Myc proteins
SIGNOR-251388
P00519
Q13315
0
phosphorylation
up-regulates
0.744
Ataxia telangiectasia mutant protein activates c-abl tyrosine kinase in response to ionizing radiation. Atm kinase domain corrects this defect, as it phosphorylates the c-abl tyrosine kinase in vitro at ser 465, leading to the activation of c-abl.
SIGNOR-48818
P61586
Q12802
0
guanine nucleotide exchange factor
up-regulates activity
0.744
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-260527
P98177
Q96EB6
0
deacetylation
up-regulates
0.744
Deacetylation of foxos involves binding of the nad-dependent deacetylase hsir2(sirt1). Accordingly, hsir2(sirt1)-mediated deacetylation precludes foxo inhibition through acetylation and thereby prolongs foxo-dependent transcription of stress-regulating genes.
SIGNOR-124714
Q9UPX8
Q9Y2H0
0
relocalization
up-regulates activity
0.744
SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).
SIGNOR-264596
Q92844
Q14164
0
phosphorylation
down-regulates activity
0.743
IKK-i phosphorylates I-TRAF. In vitro kinase assays demonstrate that IKK‐i phosphorylates I‐TRAF in the middle portion that associates with TRAF2. Interestingly, TRAF2 is freed from the I‐TRAF/TRAF2 complex after I‐TRAF phosphorylation. TRAF2 isdistributed throughout the cytoplasm, in the formof inactive an I-TRAF/TRAF2 complex
SIGNOR-262722
Q53ET0
Q9H0K1
0
phosphorylation
down-regulates
0.743
Phosphorylation on the ser171 residue of crtc2 by ampk and ampk-related kinases, including the salt-inducible kinases (siks), is critical for determining the activity, cellular localization, and degradation of crtc2
SIGNOR-142218
P84022
P24941
0
phosphorylation
down-regulates activity
0.743
In the nucleus cdk2/4-mediated phosphorylation of smad3 occurs mostly at thr8, thr179, and ser213. Cdk-dependent phosphorylation of smad3 inhibits its transcriptional activity
SIGNOR-182971
P21462
P04083
0
binding
up-regulates activity
0.743
We show that the mimetic N-terminal annexin 1 peptide Ac1-25 is able to activate and desensitize not only FPR but also FPRL1 and FPRL2.
SIGNOR-259439
P42224
Q06124
0
dephosphorylation
down-regulates activity
0.743
SHP-2 is a dual-specificity phosphatase involved in Stat1 dephosphorylation at both tyrosine and serine residues in nuclei|In SHP-2-/- mouse fibroblast cells, Stat1 phosphorylation at both the tyrosine residue Tyr(701) and the serine residue Ser(727) |Overexpression of SHP-2 in 293T cells inhibited IFNgamma-dependent Stat1 phosphorylation and suppressed Stat1-dependent induction of luciferase activity.
SIGNOR-248673
P15172
Q06413
0
binding
up-regulates activity
0.743
Myod-e protein heterodimers interact with mef2 proteins to synergistically activate myogenesis.
SIGNOR-54089
P01106
P61244
0
binding
up-regulates
0.743
In vivo transactivation assays suggest that myc-max and mad-max complexes have opposing functions in transcription and that max plays a central role in this network of transcription factors
SIGNOR-39137
O75084
P56703
0
binding
up-regulates activity
0.743
These experiments suggest that activation of the Wnt/β-catenin pathway by Wnt3 is mediated in part through FZD7 in HCC cells.
SIGNOR-280437
O00548
Q86YT6
0
ubiquitination
up-regulates activity
0.743
Mib physically interacts with Delta and promotes its ubiquitination and internalization [66], which have been shown to up-regulate Notch activity.
SIGNOR-209750
P37231
P19793
0
binding
up-regulates
0.743
Although the three ppar subtypes are closely related and bind to similar dna response elements as heterodimers with the 9-cis retinoic acid receptor rxr, each subserves a distinct physiology
SIGNOR-105445
Q14814
Q09472
0
binding
up-regulates
0.743
Once released from associated repressors, MEF2 is bound by the p300 coactivator, which possesses histone acetyltransferase activity. Thus, the net result of CaMK signaling to MEF2 complexes is increased histone acetylation (Ac), which relaxes chromatin and stimulates MEF2 target gene transcription.
SIGNOR-232162
P05412
P04150
0
transcriptional regulation
down-regulates quantity by repression
0.743
We have described how the receptor uses several means to achieve repression of the genes regulated by AP-1 and NF-KB proteins
SIGNOR-251679
P42768
Q06187
0
phosphorylation
up-regulates activity
0.743
These results demonstrate that WASP, under this experimental condition, can be tyrosine-phosphorylated by the kinase activity of Btk and that the direct interaction between WASP and the SH3 domain of Btk is required for this phosphorylation to occur.
SIGNOR-273958
P20273
P07948
0
phosphorylation
down-regulates activity
0.743
LYN is a BCR-associated SRC kinase involved in the positive regulation of BCR, but it also functions as a negative regulator by phosphorylating the immunoreceptor tyrosine-based inhibitory motifs (ITIMs) of CD22.
SIGNOR-268443
P42702
P26441
0
binding
up-regulates
0.742
Ciliary neurotrophic factor (cntf) is a cytokine supporting the differentiation and survival of various cell types in the peripheral and central nervous systems. Its receptor complex consists of a non-signaling alpha chain, cntfr, and two signaling beta chains, gp130 and the leukemia inhibitory factor receptor (lifr)
SIGNOR-81382
Q96GD4
Q9P2N7
0
binding
up-regulates activity
0.742
Aurora B Interacts with the Cul3 Complex during Mitosis and Is Ubiquitylated in a Cul3-Dependent Manner In Vivo and In Vitro. our results suggest that Cul3/KLHL9/KLHL13 activity is required to remove the chromosomal passenger protein Aurora B from mitotic chromosomes, and that Aurora B is ubiquitylated in vivo and in vitro in a KLHL9/13-dependent manner. We conclude that the Cul3/KLHL9/KLHL13 E3 ligase is an important cell-cycle regulator which, in addition to the anaphase-promoting complex (APC), coordinates mitotic progression and completion of cytokinesis.
SIGNOR-271657
P07900
O95433
0
binding
up-regulates activity
0.742
The N-terminal region of Aha1 interacts with the central domain of Hsp90 and stimulates Hsp90 ATPase activity
SIGNOR-252211
P32246
P80098
0
binding
up-regulates
0.742
For example, 11 chemokines are reported to bind to CC chemokine receptor (CCR) 1, including macrophage inflammatory protein (MIP)‐1α , MIP‐1β, MIP‐1δ, regulated upon activation, normal T cell‐expressed and secreted (RANTES), monocyte chemotactic peptide (MCP)‐1, MCP‐2, MCP‐3, MCP‐4, leukotactin‐1 (Lkn‐1), myeloid progenitor inhibitory factor (MPIF)‐1, and hemofiltrate CC chemokine (HCC)‐1
SIGNOR-254368
P27361
P36507
0
phosphorylation
up-regulates
0.742
The primary structure of mek, a protein kinase that phosphorylates the erk gene product
SIGNOR-19244
Q06413
Q09472
0
binding
up-regulates
0.742
Once released from associated repressors, MEF2 is bound by the p300 coactivator, which possesses histone acetyltransferase activity. Thus, the net result of CaMK signaling to MEF2 complexes is increased histone acetylation (Ac), which relaxes chromatin and stimulates MEF2 target gene transcription.
SIGNOR-232159
Q9UQC2
Q06124
0
dephosphorylation
down-regulates
0.742
Expression of the gab2 tyr-614-->phe (y614f) mutant, defective in shp-2 association, prevents erk (extracellular-signal-regulated kinase) activation and expression of a luciferase reporter plasmid driven by the c-fos sre (serum response element), indicating that interaction of shp-2 with gab2 is required for erk activation in response to il-2.
SIGNOR-124958
P61006
O15078
0
binding
up-regulates activity
0.742
CEP290 cooperates with Rab8a to promote ciliogenesis and this function is antagonized by CP110. CEP290 recruits Rab8a to centrosomes. Depletion of CEP290 results in a significant decrease of Rab8a at the centrosome and at the cilium, raising the possibility that CEP290 first recruits Rab8a through direct protein-protein interactions to the centrosome in cycling cells and later promotes ciliogenesis by allowing the entry of Rab8a into the cilium
SIGNOR-252146
Q9HAW4
O00311
0
phosphorylation
up-regulates activity
0.742
Cdc7 phosphorylates Claspin in a manner dependent on AP and inhibits N\u2013C interaction.|Thus, Cdc7-ASK may activate DNA and PCNA bindings of Claspin through AP-mediated phosphorylation.
SIGNOR-279360
P55210
Q14790
0
cleavage
up-regulates
0.742
Casp8 can activate downstream caspases like caspase-6, and caspase-7 by directly cleaving them.
SIGNOR-58118
P15172
Q02078
0
binding
up-regulates activity
0.742
Myod-e protein heterodimers interact with mef2 proteins to synergistically activate myogenesis.
SIGNOR-54086
P04637
Q13535
0
phosphorylation
up-regulates quantity by stabilization
0.742
Nhibition of atr kinase activity substantially reduces hypoxia-induced phosphorylation of p53 protein on serine 15 as well as p53 protein accumulation.
SIGNOR-115134
Q15796
P12755
0
binding
down-regulates activity
0.741
The ski and snon protein family associate with and repress the activity of smad2, smad3, and smad4, three members of the tgf-fl signaling pathway
SIGNOR-236155
Q14653
Q14164
0
phosphorylation
up-regulates activity
0.741
Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404.
SIGNOR-178379
P84022
P36896
0
phosphorylation
up-regulates activity
0.741
ActRIIB, and then partners with a type I receptor, either activin receptor-like kinase 4 (ALK4 or ActRIB) or ALK5 (T²RI), to induce phosphorylation of Smad2/Smad3 and activate a TGF-²-like signaling pathway
SIGNOR-235160
Q9UQK1
Q6VVB1
0
ubiquitination
down-regulates quantity by destabilization
0.741
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-276238
Q71F23
P53350
0
phosphorylation
down-regulates
0.741
S77 and t78 of pbip1 are important for plk1-dependent pbip1 phosphorylation and degradation. Here, we demonstrate that a pbd-binding protein, pbip1, is crucial for recruiting plk1 to the interphase and mitotic kinetochores. Unprecedentedly, plk1 phosphorylated pbip1 at t78. Later in mitosis, plk1 also induced pbip1 degradation in a t78-dependent manner, thereby enabling itself to interact with other components critical for proper kinetochore functions
SIGNOR-150457
Q9H0R8
Q14596
0
binding
up-regulates
0.741
We performed glutathione s-transferase (gst) pull-down assays using extracts from hek293 cells overexpressing an ha-tagged nbr1(d50r) mutant, which lacks the ability to bind p62 (lamark et al., 2003) (figures s1a and s1b, available online), and gst fusions of six human atg8 homologs: gabarap, gabarapl1, gabarapl2, lc3a, lc3b, and lc3c. Indeed, nbr1 interacted with all these members of the mammalian atg8 protein family
SIGNOR-184264
P04637
Q93009
0
deubiquitination
up-regulates
0.741
Hausp counteracts the destabilizing effect of mdm2 by direct deubiquitination of p53.
SIGNOR-139456
P60520
Q14596
0
binding
up-regulates
0.741
We performed glutathione s-transferase (gst) pull-down assays using extracts from hek293 cells overexpressing an ha-tagged nbr1(d50r) mutant, which lacks the ability to bind p62 (lamark et al., 2003) (figures s1a and s1b, available online), and gst fusions of six human atg8 homologs: gabarap, gabarapl1, gabarapl2, lc3a, lc3b, and lc3c. Indeed, nbr1 interacted with all these members of the mammalian atg8 protein family.
SIGNOR-184267
Q9UKG1
Q86V24
0
binding
up-regulates
0.741
Appl1 interacts with adiponectin receptors in mammalian cells and the interaction is stimulated by adiponectin.
SIGNOR-146215
P60484
Q93009
0
deubiquitination
down-regulates activity
0.741
BCR-ABL disrupts PTEN nuclear-cytoplasmic shuttling through phosphorylation-dependent activation of HAUSP|hese data indicate that BCR-ABL phosphorylation of HAUSP modulates HAUSP’s deubiquitinase activity toward PTEN.
SIGNOR-276533
P36897
O43541
0
binding
down-regulates activity
0.74
The inhibitory Smads (I-Smads), i.e. Smad6 and Smad7, are negative regulators of transforming growth factor-_ (TGF-_) family signaling. I-Smads inhibit TGF-_ family signaling principally through physical interaction with type I receptors (activin receptor-like kinases), so as to compete with receptor-regulated Smads (R-Smads) for activation.
SIGNOR-167160
P19838
P25963
0
binding
down-regulates activity
0.74
Nf-kappa b is an inducible transcription factor comprised of a 50-kd (p50) and a 65-kd (p65) subunit. Induction of nf-kappa b activity, which is a critical event in many signal transduction pathways, involves release from a cytoplasmic inhibitory protein, i kappa b, followed by translocation of the active transcription factor complex into the nucleus. we demonstrate by in vitro and in vivo methods that the recently cloned i kappa b/mad-3 interacts with both the p50 and p65 subunits of nf-kappa b
SIGNOR-17688
Q7L523
Q8N8N0
0
polyubiquitination
down-regulates activity
0.74
 Here, we identified the lysosome-anchored E3 ubiquitin ligase RNF152 as an essential negative regulator of the mTORC1 pathway by targeting RagA for K63-linked ubiquitination. RNF152 interacts with and ubiquitinates RagA in an amino-acid-sensitive manner. The mutation of RagA ubiquitination sites abolishes this effect of RNF152 and enhances the RagA-mediated activation of mTORC1. Ubiquitination by RNF152 generates an anchor on RagA to recruit its inhibitor GATOR1, a GAP complex for Rag GTPases. 
SIGNOR-272222
P56645
P49674
0
phosphorylation
down-regulates activity
0.74
The CKI phosphorylation of mPer1 and mPer3 proteins results in their rapid degradation, which is dependent on the ubiquitin-proteasome pathway. Moreover, CKIepsilon and CKIdelta are able to induce nuclear translocation of mPer3, which requires its nuclear localization signal. The mutation in potential phosphorylation sites on mPer3 decreased the extent of both nuclear translocation and degradation of mPer3 that are stimulated by CKIepsilon. | In mut7 in which all of the conserved serine and threonine residues in this region were mutated, the ratio of the shifted band was greatly reduced reproducibly. 
SIGNOR-250816
Q15761
P01303
0
binding
up-regulates
0.74
Npy expression significantly increases whereas the gene expression of its receptors npy1r, npy2r, and npy5r initially decreases.
SIGNOR-114746
Q14186
O00716
0
binding
up-regulates activity
0.74
The transcriptionally active forms of E2F are heterodimers composed of one polypeptide encoded by the E2F gene family and one polypeptide encoded by the DP gene family.In transfected cells, DP-1 did not accumulate in the nucleus unless it was coexpressed with the heterodimeric partners E2F-1, E2F-2, or E2F-3.
SIGNOR-240553
P25025
P19875
0
binding
up-regulates activity
0.74
CXCL2/3, also known as macrophage inflammatory protein-2α/2β (MIP-2α/MIP-2β), share the same receptor CXCR2 with CXCL1 and are able to activate neutrophils effectively
SIGNOR-277718
P46108
P00533
0
phosphorylation
down-regulates activity
0.74
To address these questions, we have developed an antibody that specifically recognizes the CrkII protein phosphorylated on Tyr221, and we found that the EGF receptor directly phosphorylates CrkII on Tyr221. Furthermore, we observed that the phosphorylation of Tyr221 of CrkII correlated with its dissociation from the EGF receptor, implicating the phosphorylation of Tyr221 in the negative feedback of binding to the EGF receptor.
SIGNOR-251091
P49757
Q8TBB1
0
ubiquitination
down-regulates
0.74
Lnx functions as a ring type e3 ubiquitin ligase that targets the cell fate determinant numb for ubiquitin-dependent degradation.
SIGNOR-112201
P35568
O14543
0
binding
down-regulates
0.74
Irs-1 is the major signaling protein that socs3 targets to inhibit insulin signaling
SIGNOR-199361
Q02750
P10398
0
phosphorylation
up-regulates
0.74
Our data demonstrated that a-raf is, indeed, a mek1 activator and may play a role in growth factor signaling|The immunoprecipitates were assayed for GST-MEK1 activation. D, activation of MEK1 by A-Raf requires the presence of serine residue 218 and 222.
SIGNOR-235944
O00187
P11226
0
binding
up-regulates activity
0.74
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-263415
P10636
P49841
0
phosphorylation
down-regulates activity
0.739
We found that cdk5 phosphorylated tau(441) at Thr-181, Ser-199, Ser-202, Thr-205, Thr-212, Ser-214, Thr-217, Thr-231, Ser-235, Ser-396, and Ser-404, but not at Ser-262, Ser-400, Thr-403, Ser-409, Ser-413, or Ser-422. GSK-3beta phosphorylated all the cdk5-catalyzed sites above except Ser-235.
SIGNOR-249346
P25054
Q5JTC6
0
relocalization
up-regulates
0.739
Apc membrane recruitment protein 1 (amer1;alsoknownas wtx)
SIGNOR-199375
P46531
P78536
0
cleavage
up-regulates activity
0.739
... here we show that an additional processing event occurs in the extracellular part of the receptor, preceding cleavage by the gamma-secretase-like activity. Purification of the activity accounting for this cleavage in vitro shows that it is due to tace (tnfalpha-converting enzyme), a member of the adam (a disintegrin and metalloprotease domain) family of metalloproteases.
SIGNOR-78903
P15336
P27361
0
phosphorylation
up-regulates
0.739
Here, we show that in fibroblasts, insulin, epidermal growth factor (egf) and serum activate atf2 via a so far unknown two-step mechanism involving two distinct ras effector pathways: the raf-mek-erk pathway induces phosphorylation of atf2 thr71, whereas subsequent atf2 thr69 phosphorylation requires the ral-ralgds-src-p38 pathway.
SIGNOR-90533
Q9UQB8
P63000
0
binding
up-regulates
0.739
Here we demonstrate that irsp53, a substrate for insulin receptor with unknown function, is the 'missing link' between rac and wave. Activated rac binds to the amino terminus of irsp53, and carboxy-terminal src-homology-3 domain of irsp53 binds to wave to form a trimolecular complex.
SIGNOR-85302
Q01726
P42127
0
binding
down-regulates activity
0.739
The antagonist agouti signal protein (ASP) interacts with the Mc1r and blocks its stimulation by MSH.
SIGNOR-252378
Q14457
P10415
0
binding
down-regulates
0.739
In mammalian cells, the antiapoptotic protein, bcl-2, binds to beclin 1 during nonstarvation conditions and inhibits its autophagy function.
SIGNOR-156941
P60953
Q96N67
0
guanine nucleotide exchange factor
up-regulates activity
0.739
As a GEF, Dock7 exchanges GDP for GTP on Cdc42 and Rac1, causing their activation, followed by activation of downstream effectors, including the dephosphorylation (activation) of cofilin, a key regulator of actin turnover.
SIGNOR-261886
P08069
Q13322
0
binding
down-regulates
0.739
Grb10 negatively regulates growth factor signaling. It binds the insulinand insulin-like growth factor 1 (igf-1) receptors, and mice without grb10 are larger and exhibit enhanced insulin sensitivity
SIGNOR-174062
Q9Y4K3
P58753
0
binding
up-regulates activity
0.739
Mal interaction with TRAF6 is required for NF-κB transactivation
SIGNOR-280461
Q9Y6K9
Q13315
0
phosphorylation
down-regulates activity
0.739
Atm phosphorylates serine-85 of nemo to promote its ubiquitin-dependent nuclear export.
SIGNOR-144813
Q9UHI6
P41162
0
transcriptional regulation
down-regulates quantity by repression
0.739
ETV3 target genes including etv3, ddx20, and dusp6 provide negative feedback regulation of ETV3 production and activity. Negative feedback along with constitutive instability may serve to tightly regulate ETV3 abundance. Our date suggest that phosphorylation by ERK2 relieves repression by ETV3, allowing activation of cell cycle control genes including myc, components of the NF-κB pathway, and genes required form RNA processing and translation.
SIGNOR-262779
Q15628
Q93038
0
binding
up-regulates
0.739
Dr3 induces apoptosis by tradd-mediated recruitment of fadd and caspase-8
SIGNOR-100480
P60953
Q9NR80
0
guanine nucleotide exchange factor
up-regulates activity
0.739
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-260532
P24928
Q8IXW5
0
dephosphorylation
up-regulates activity
0.738
In addition, we show that RPAP2 is a CTD Ser5 phosphatase. Taken together, our results indicate that during transcription of snRNA genes, Ser7 phosphorylation facilitates recruitment of RPAP2, which in turn both recruits Integrator and dephosphorylates Ser5.|The Pol II CTD is first phosphorylated on Ser5 and then on Ser7 by CDK7. RPAP2 associates with the Pol II CTD after Ser7 phosphorylation and tethers a subcomplex of Integrator to snRNA genes. RPAP2 dephosphorylates Ser5P of the CTD, facilitating transcription and the subsequent recruitment of the Int11 catalytic subunit of Integrator
SIGNOR-248748