| + |
PRKCE | up-regulates activity 
phosphorylation
|
SHC1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263048 |
Ser139 |
EEWTRHGsFVNKPTR |
Mus musculus |
NIH-3T3 Cell |
| pmid |
sentence |
| 12052829 |
Among them, Ser(29) in p52(Shc) (equivalent to Ser(138) in p66(Shc)) was phosphorylated only after TPA stimulation. Phosphorylation of this site together with the intact phosphotyrosine-binding domain was essential for ShcA binding to the protein-tyrosine phosphatase PTP-PEST. TPA-induced ShcA phosphorylation at this site (and hence, its association with PTP-PEST) was inhibited by a protein kinase C-specific inhibitor and was induced by overexpression of constitutively active mutants of protein kinase Calpha, -epsilon, and -delta isoforms. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
PRKCD | up-regulates
phosphorylation
|
SHC1 |
0.559 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-149398 |
Ser139 |
EEWTRHGsFVNKPTR |
Homo sapiens |
|
| pmid |
sentence |
| 16963224 |
Pkc delta phosphorylates p52shca at ser29 to regulate erk activation in response to h2o2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PRKCA | up-regulates activity
phosphorylation
|
SHC1 |
0.404 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249150 |
Ser139 |
EEWTRHGsFVNKPTR |
Mus musculus |
|
| pmid |
sentence |
| 12052829 |
Among them, Ser(29) in p52(Shc) (equivalent to Ser(138) in p66(Shc)) was phosphorylated only after TPA stimulation. Phosphorylation of this site together with the intact phosphotyrosine-binding domain was essential for ShcA binding to the protein-tyrosine phosphatase PTP-PEST. TPA-induced ShcA phosphorylation at this site (and hence, its association with PTP-PEST) was inhibited by a protein kinase C-specific inhibitor and was induced by overexpression of constitutively active mutants of protein kinase Calpha, -epsilon, and -delta isoforms. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263047 |
Ser139 |
EEWTRHGsFVNKPTR |
Mus musculus |
NIH-3T3 Cell |
| pmid |
sentence |
| 12052829 |
Among them, Ser(29) in p52(Shc) (equivalent to Ser(138) in p66(Shc)) was phosphorylated only after TPA stimulation. Phosphorylation of this site together with the intact phosphotyrosine-binding domain was essential for ShcA binding to the protein-tyrosine phosphatase PTP-PEST. TPA-induced ShcA phosphorylation at this site (and hence, its association with PTP-PEST) was inhibited by a protein kinase C-specific inhibitor and was induced by overexpression of constitutively active mutants of protein kinase Calpha, -epsilon, and -delta isoforms. |
|
| Publications: |
2 |
Organism: |
Mus Musculus |
| + |
PRKCD |
phosphorylation
|
SHC1 |
0.559 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-149402 |
Ser28 |
LEEGASGsTPPEELP |
Homo sapiens |
|
| pmid |
sentence |
| 16963224 |
Activated pkc delta was able to phosphorylate shca at ser29, as determined by mass spectrometry. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SYK | up-regulates
phosphorylation
|
SHC1 |
0.761 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-59635 |
Tyr349 |
EEPPDHQyYNDFPGK |
Homo sapiens |
T-lymphocyte |
| pmid |
sentence |
| 9710204 |
The syk-family kinases (syk and zap-70) were able to phosphorylate the y239 and y240 sites, and less efficiently the y317 site on sch1 (iso2). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-59639 |
Tyr350 |
EPPDHQYyNDFPGKE |
Homo sapiens |
T-lymphocyte |
| pmid |
sentence |
| 9710204 |
The syk-family kinases (syk and zap-70) were able to phosphorylate the y239 and y240 sites, and less efficiently the y317 site on sch1 (iso2). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-59643 |
Tyr427 |
ELFDDPSyVNVQNLD |
Homo sapiens |
T-lymphocyte |
| pmid |
sentence |
| 9710204 |
The syk-family kinases (syk and zap-70) were able to phosphorylate the y239 and y240 sites, and less efficiently the y317 site on sch1 (iso2). |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
SRC | up-regulates activity
phosphorylation
|
SHC1 |
0.659 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-44866 |
Tyr349 |
EEPPDHQyYNDFPGK |
Homo sapiens |
|
| pmid |
sentence |
| 8939605 |
Here, we report the identification of two major and novel Shc tyrosine phosphorylation sites, Y239 and Y240. Y239/240 are co-ordinately phosphorylated by the src protein-tyrosine kinase in vitro, and in response to epidermal growth factor stimulation or in v-src-transformed cells in vivo. phosphorylation of y317 has been implicated in grb2 binding and activation of the ras pathway. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-44870 |
Tyr350 |
EPPDHQYyNDFPGKE |
Homo sapiens |
|
| pmid |
sentence |
| 8939605 |
Here, we report the identification of two major and novel Shc tyrosine phosphorylation sites, Y239 and Y240. Y239/240 are co-ordinately phosphorylated by the src protein-tyrosine kinase in vitro, and in response to epidermal growth factor stimulation or in v-src-transformed cells in vivo. phosphorylation of y317 has been implicated in grb2 binding and activation of the ras pathway. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | EGFR Signaling, IL6 Signaling |
| + |
PTPN2 | down-regulates activity 
dephosphorylation
|
SHC1 |
0.562 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248397 |
Tyr349 |
EEPPDHQyYNDFPGK |
Homo sapiens |
|
| pmid |
sentence |
| 9488479 |
However, TC45 inhibited the EGF-induced association of p52Shc with Grb2, which was attributed to the ability of the PTP to recognize specifically p52Shc phosphorylated on Y239. These results indicate that TC45 recognizes not only selected substrates in a cellular context but also specific sites within substrates and thus may regulate discrete signaling events. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PTPN12 | down-regulates
dephosphorylation
|
SHC1 |
0.669 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-44361 |
Tyr349 |
EEPPDHQyYNDFPGK |
Homo sapiens |
|
| pmid |
sentence |
| 8939605 |
The shc adaptor protein is highly phosphorylated at conserved, twin tyrosine residues (y239/240) that mediate protein-protein interactions. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-44862 |
Tyr350 |
EPPDHQYyNDFPGKE |
Homo sapiens |
|
| pmid |
sentence |
| 8939605 |
The shc adaptor protein is highly phosphorylated at conserved, twin tyrosine residues (y239/240) that mediate protein-protein interactions. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
FLT4 |
phosphorylation
|
SHC1 |
0.582 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-64186 |
Tyr349 |
EEPPDHQyYNDFPGK |
Homo sapiens |
|
| pmid |
sentence |
| 9927207 |
We have investigated which of the shc tyrosine residues are targeted by the vegfr3/ flt4 kinase and the role of the shc ptb and sh2 domains in this process. Our results show that y239/ y240 and y313 are simultaneously phosphorylated by the kinase, creating grb2 binding sites. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-64076 |
Tyr350 |
EPPDHQYyNDFPGKE |
Homo sapiens |
|
| pmid |
sentence |
| 9927207 |
We have investigated which of the shc tyrosine residues are targeted by the vegfr3/ flt4 kinase and the role of the shc ptb and sh2 domains in this process. Our results show that y239/ y240 and y313 are simultaneously phosphorylated by the kinase, creating grb2 binding sites. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-64190 |
Tyr427 |
ELFDDPSyVNVQNLD |
Homo sapiens |
|
| pmid |
sentence |
| 9927207 |
We have investigated which of the shc tyrosine residues are targeted by the vegfr3/ flt4 kinase and the role of the shc ptb and sh2 domains in this process. Our results show that y239/ y240 and y313 are simultaneously phosphorylated by the kinase, creating grb2 binding sites. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
ZAP70 | up-regulates
phosphorylation
|
SHC1 |
0.671 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-59647 |
Tyr349 |
EEPPDHQyYNDFPGK |
Homo sapiens |
T-lymphocyte |
| pmid |
sentence |
| 9710204 |
The syk-family kinases (syk and zap-70) were able to phosphorylate the y239 and y240 sites, and less efficiently the y317 site on shc1 (iso2). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-59651 |
Tyr350 |
EPPDHQYyNDFPGKE |
Homo sapiens |
T-lymphocyte |
| pmid |
sentence |
| 9710204 |
The syk-family kinases (syk and zap-70) were able to phosphorylate the y239 and y240 sites, and less efficiently the y317 site on shc1 (iso2). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-59659 |
Tyr427 |
ELFDDPSyVNVQNLD |
Homo sapiens |
T-lymphocyte |
| pmid |
sentence |
| 9710204 |
The syk-family kinases (syk and zap-70) were able to phosphorylate the y239 and y240 sites, and less efficiently the y317 site on shc1 (iso2). |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
FYN | up-regulates
phosphorylation
|
SHC1 |
0.729 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-59623 |
Tyr349 |
EEPPDHQyYNDFPGK |
Homo sapiens |
T-lymphocyte |
| pmid |
sentence |
| 9710204 |
Syk and zap-70 were able to phosphorylate the y239 and y240 sites, and less efficiently the y317 site. Of the two potential grb2 binding sites (y239 and y317), y239 appears to play a greater role in recruiting sos through grb2. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-59627 |
Tyr350 |
EPPDHQYyNDFPGKE |
Homo sapiens |
T-lymphocyte |
| pmid |
sentence |
| 9710204 |
Syk and zap-70 were able to phosphorylate the y239 and y240 sites, and less efficiently the y317 site. Of the two potential grb2 binding sites (y239 and y317), y239 appears to play a greater role in recruiting sos through grb2. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-60160 |
Tyr427 |
ELFDDPSyVNVQNLD |
Homo sapiens |
|
| pmid |
sentence |
| 9741627 |
Shc is subsequently phosphorylated at tyrosine 317 and recruits grb2 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-59631 |
Tyr427 |
ELFDDPSyVNVQNLD |
Homo sapiens |
T-lymphocyte |
| pmid |
sentence |
| 9710204 |
Syk and zap-70 were able to phosphorylate the y239 and y240 sites, and less efficiently the y317 site. Of the two potential grb2 binding sites (y239 and y317), y239 appears to play a greater role in recruiting sos through grb2. |
|
| Publications: |
4 |
Organism: |
Homo Sapiens |
| + |
PTPRG | down-regulates activity
dephosphorylation
|
SHC1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254723 |
Tyr349 |
EEPPDHQyYNDFPGK |
in vitro |
|
| pmid |
sentence |
| 25624455 |
PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254724 |
Tyr350 |
EPPDHQYyNDFPGKE |
in vitro |
|
| pmid |
sentence |
| 25624455 |
PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity. |
|
| Publications: |
2 |
Organism: |
In Vitro |
| + |
FLT3 | up-regulates activity
phosphorylation
|
SHC1 |
0.442 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251146 |
Tyr349 |
EEPPDHQyYNDFPGK |
Homo sapiens |
|
| pmid |
sentence |
| 10482988 |
Intracellular FLT3 signaling involves tyrosine phosphorylation of several cytoplasmic proteins including SHC. We have found that upon FLT3 activation SHC phosphorylation occurs at tyrosine 239/240 and 313. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251147 |
Tyr350 |
EPPDHQYyNDFPGKE |
Homo sapiens |
|
| pmid |
sentence |
| 10482988 |
Intracellular FLT3 signaling involves tyrosine phosphorylation of several cytoplasmic proteins including SHC. We have found that upon FLT3 activation SHC phosphorylation occurs at tyrosine 239/240 and 313. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251148 |
Tyr427 |
ELFDDPSyVNVQNLD |
Homo sapiens |
|
| pmid |
sentence |
| 10482988 |
Intracellular FLT3 signaling involves tyrosine phosphorylation of several cytoplasmic proteins including SHC. We have found that upon FLT3 activation SHC phosphorylation occurs at tyrosine 239/240 and 313. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261540 |
|
|
Mus musculus |
32D Cell |
| pmid |
sentence |
| 15769897 |
we observed constitutive activation of Erk-1 and Erk-2, Akt, and of Shc by both Flt3-ITD and Flt3-D835Y |
|
| Publications: |
4 |
Organism: |
Homo Sapiens, Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, miRNA in AML, FLT3-ITD in AML |
| + |
LCK | up-regulates activity
phosphorylation
|
SHC1 |
0.742 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251388 |
Tyr427 |
ELFDDPSyVNVQNLD |
Homo sapiens |
T-lymphocyte |
| pmid |
sentence |
| 9710204 |
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 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PTK2 | up-regulates activity
phosphorylation
|
SHC1 |
0.671 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259854 |
Tyr427 |
ELFDDPSyVNVQNLD |
Homo sapiens |
|
| pmid |
sentence |
| 9566877 |
In vitro, FAK directly phosphorylated Shc Tyr-317 to promote Grb2 binding. FAK can associate and directly phosphorylate Shc at Tyr-317 to promote Grb2 binding and low-level signaling to ERK2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
INSR | up-regulates activity
phosphorylation
|
SHC1 |
0.706 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251325 |
Tyr427 |
ELFDDPSyVNVQNLD |
|
|
| pmid |
sentence |
| 11075717 |
Insulin predominantly phosphorylates the Shc Tyr-317 residue. Phosphorylated Shc binds to Grb2 which forms a complex with Sos guanine nucleotide exchange factor for p21ras. |
|
| Publications: |
1 |
| + |
TGFBR1 | up-regulates
phosphorylation
|
SHC1 |
0.541 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227503 |
|
|
Mus musculus |
Swiss-3T3 Cell |
| pmid |
sentence |
| 17673906 |
We now report that upon TGF-_ stimulation, T_RI phosphorylates ShcA on serine and, to a lesser degree, on tyrosine to activate Erk MAP kinases. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Thyroid cancer |
| + |
SHC1 | up-regulates
binding
|
GRAP |
0.51 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-45528 |
|
|
Homo sapiens |
T-lymphocyte |
| pmid |
sentence |
| 8995379 |
T cell activation effects an increase in grap association with p36/38, shc, sos, and dynamin. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
EGFR | up-regulates
binding
|
SHC1 |
0.912 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235481 |
|
|
Mus musculus |
NIH-3T3 Cell |
| pmid |
sentence |
| 7518560 |
Both competition experiments with synthetic phosphopeptides and dephosphorylation protection analysis demonstrated that y-1173 and y-992 are major and minor binding sites, respectively, for shc on the egfr. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, EGFR Signaling, FLT3-ITD in AML, Noonan syndrome |
| + |
NTRK1 | up-regulates
binding
|
SHC1 |
0.836 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-75408 |
|
|
Homo sapiens |
Neuron |
| pmid |
sentence |
| 10708759 |
Autophosphorylated trka binds directly to plc?, Abl, and shc. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SHC1 | up-regulates
binding
|
GRB2 |
0.964 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235615 |
|
|
Sus scrofa |
Porcine Aortic Endothelial Cell |
| pmid |
sentence |
| 10523831 |
Phosphorylation of the adapter protein shc by growth factor receptors provides association sites for grb2-sos, thereby activating the ras/map kinase pathway. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236236 |
|
|
Homo sapiens |
T-lymphocyte, Leukemia Cell, Lymphoma Cell |
| pmid |
sentence |
| 24737791 |
The signaling mechanism utilizes an adaptor protein, shc, which binds to a phosphotyrosine residue on the il-2/15r?, Resulting in activation of grb2 and onto akt via the shc-grb2-gab2-pi3k-akt signaling pathway to increase cell proliferation and/or survival |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236366 |
|
|
Mus musculus |
Swiss-3T3 Cell |
| pmid |
sentence |
| 17673906 |
TGF-beta-induced ShcA phosphorylation induces ShcA association with Grb2 and Sos, thereby initiating the well-characterised pathway linking receptor tyrosine kinases with Erk MAP kinases. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235881 |
|
|
Homo sapiens |
B-lymphocyte |
| pmid |
sentence |
| 10207047 |
The results indicate that ship, shc, and grb2 form a ternary complex in stimulated b cells, with grb2 stabilizing the interaction between shc and ship. The interactions between shc, grb2, and ship are therefore analogous to the interactions between shc, grb2, and sos. Shc and grb2 may help to localize ship to the cell membrane, regulating ship's inhibitory function following bcr stimulation. |
|
| Publications: |
4 |
Organism: |
Sus Scrofa, Homo Sapiens, Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, EGFR Signaling, IL6 Signaling, Noonan syndrome, Thyroid cancer |
| + |
SHC1 | up-regulates
binding
|
INPP5D |
0.691 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-66949 |
|
|
Homo sapiens |
B-lymphocyte |
| pmid |
sentence |
| 10207047 |
The results indicate that ship, shc, and grb2 form a ternary complex in stimulated b cells, with grb2 stabilizing the interaction between shc and ship. The interactions between shc, grb2, and ship are therefore analogous to the interactions between shc, grb2, and sos. Shc and grb2 may help to localize ship to the cell membrane, regulating ship's inhibitory function following bcr stimulation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, miRNA in AML |
| + |
SHC1 | up-regulates activity 
|
Gbeta |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-269903 |
|
|
Mus musculus |
NIH-3T3 Cell |
| pmid |
sentence |
| 17673906 |
We report that upon TGF__ stimulation, the activated TGF__ type I receptor (T_RI) recruits and directly phosphorylates ShcA proteins on tyrosine and serine. This dual phosphorylation results from an intrinsic T_RI tyrosine kinase activity that complements its well_defined serine_threonine kinase function. TGF___induced ShcA phosphorylation induces ShcA association with Grb2 and Sos, thereby initiating the well_characterised pathway linking receptor tyrosine kinases with Erk MAP kinases. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
IGF1R | up-regulates activity
binding
|
SHC1 |
0.733 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262587 |
|
|
in vitro |
|
| pmid |
sentence |
| 7541045 |
In our present work, we show that both IRS-1 and SHC interact directly with the juxtamembrane region of the IGFIR in a phosphotyrosine-dependent manner. |We propose a model in which IGFIR autophosphorylation of Tyr-950 forms a direct binding site for the amino-terminal receptor binding domains of SHC and IRS-1. This interaction is presumed to facilitate tyrosine phosphorylation of SHC on Tyr-317 leading to GRB2/SOS interaction |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
DDR2 | up-regulates
binding
|
SHC1 |
0.397 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-140724 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16186108 |
Collectively, our findings are consistent with the following mechanism for src-dependent ddr2 activation and signaling: 1) ligand binding promotes phosphorylation of tyr-740 in the ddr2 activation loop by src;2) tyr-740 phosphorylation stimulates intramolecular autophosphorylation of ddr2;3) ddr2 autophosphorylation generates cytosolic domain phosphotyrosines that promote the formation of ddr2 cytosolic domain-shc signaling complexes. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NTRK3 | up-regulates
binding
|
SHC1 |
0.723 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-65958 |
|
|
Homo sapiens |
Neuron |
| pmid |
sentence |
| 10092678 |
We demonstrate that the phosphotyrosine binding domain of frs-2 directly binds the trk receptors at the same phosphotyrosine residue that binds the signaling adapter shc, suggesting a model in which competitive binding between frs-2 and shc regulates differentiation versus proliferation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PDGFRB | up-regulates
phosphorylation
|
SHC1 |
0.654 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-36906 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 8195171 |
In this study, we have characterized the interaction between the pdgf beta-receptor and shc. multiple autophosphorylation sites in the pdgf beta-receptor are responsible for the binding of shc. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ALK | up-regulates
phosphorylation
|
SHC1 |
0.458 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-91534 |
|
|
Homo sapiens |
Lymphoma Cell |
| pmid |
sentence |
| 12185581 |
Anaplastic lymphoma kinase (alk), which turned out to be one of these phosphoproteins, was constitutively activated and associated with the ptb domain of shcc in three neuroblastoma cells. In vitro kinase assay revealed that shcc is a potent substrate of the activated alk kinase. The alk gene locus was significantly amplified in both of these cell lines, suggesting that gene amplification leads to constitutive activation of the alk kinase, which results in hyperphosphorylation of shcc. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
KDR | up-regulates activity
relocalization
|
SHC1 |
0.708 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261949 |
|
|
Sus scrofa domesticus |
Porcine Aortic Endothelial Cell |
| pmid |
sentence |
| 9405464 |
In a similar fashion, KDR associates with Grb2 and Nck in a ligand-dependent fashion, suggesting Shc, Grb2, and Nck as potential candidates involved in the regulation of endothelial function. |
|
| Publications: |
1 |
Organism: |
Sus Scrofa Domesticus |
| + |
EPHA2 | up-regulates
binding
|
SHC1 |
0.606 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-94804 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12400011 |
We also show that the interaction of epha2 with grb2 is indirect and mediated by shc and that this complex is necessary for epha2-mediated activation of erk kinases. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
EGFR | up-regulates activity
binding
|
SHC1 |
0.912 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-107712 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11350724 |
Adaptors such as Shc, Grb2, Crk or the recently characterised Dok-R protein (Jones Dumont 1999) show a modular structure containing protein protein interaction domains and putative phosphorylation sites and act as signalling platforms which extend the receptors repertoire of activated intracellular pathways. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, EGFR Signaling, FLT3-ITD in AML, Noonan syndrome |
| + |
TGFB1 | up-regulates activity
|
SHC1 |
0.447 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-242631 |
|
|
Mus musculus |
NIH-3T3 Cell |
| pmid |
sentence |
| 17673906 |
We report that upon TGF__ stimulation, the activated TGF__ type I receptor (T_RI) recruits and directly phosphorylates ShcA proteins on tyrosine and serine. This dual phosphorylation results from an intrinsic T_RI tyrosine kinase activity that complements its well_defined serine_threonine kinase function. TGF___induced ShcA phosphorylation induces ShcA association with Grb2 and Sos, thereby initiating the well_characterised pathway linking receptor tyrosine kinases with Erk MAP kinases. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Thyroid cancer |
| + |
SHC1 | up-regulates
binding
|
SOS1 |
0.77 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236363 |
|
|
Mus musculus |
Swiss-3T3 Cell |
| pmid |
sentence |
| 17673906 |
TGF-beta-induced ShcA phosphorylation induces ShcA association with Grb2 and Sos, thereby initiating the well-characterised pathway linking receptor tyrosine kinases with Erk MAP kinases. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, EGFR Signaling, IL6 Signaling, Noonan syndrome, Thyroid cancer |
| + |
ELE1-RET | up-regulates activity
binding
|
SHC1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251985 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16946010 |
RET/PTC is tumorigenic in thyroid follicular cells; it transforms thyroid cells in culture and gives rise to thyroid carcinomas in transgenic mice. effects of RET/PTC activation require signaling along the MAPK pathway and, more specifically, the presence of the functional BRAF kinase. all breakpoints in the RET gene occur within intron 11, leaving intact the TK domain of the receptor and enabling the RET/PTC oncoprotein to bind SHC via Y1062 and activate the RAS-RAF-MAPK cascade |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Thyroid cancer |
| + |
ERBB2 | up-regulates
binding
|
SHC1 |
0.802 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-65579 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10085134 |
Shc interacts with and is an excellent substrate for erbb2 and appears to play an important role in mitogenic signaling through this receptor tyrosine kinase |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SHC1 | up-regulates activity
|
MAPK3 |
0.63 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-242625 |
|
|
Mus musculus |
NIH-3T3 Cell |
| pmid |
sentence |
| 17673906 |
We report that upon TGF__ stimulation, the activated TGF__ type I receptor (T_RI) recruits and directly phosphorylates ShcA proteins on tyrosine and serine. This dual phosphorylation results from an intrinsic T_RI tyrosine kinase activity that complements its well_defined serine_threonine kinase function. TGF___induced ShcA phosphorylation induces ShcA association with Grb2 and Sos, thereby initiating the well_characterised pathway linking receptor tyrosine kinases with Erk MAP kinases. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
INSR | up-regulates
binding
|
SHC1 |
0.706 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-84251 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11075717 |
The npxy motif around 960-tyr residue of the insulin receptor binds to the n-terminal ptb domain of shc. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CCDC6-RET | up-regulates activity
binding
|
SHC1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251986 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16946010 |
RET/PTC is tumorigenic in thyroid follicular cells; it transforms thyroid cells in culture and gives rise to thyroid carcinomas in transgenic mice. effects of RET/PTC activation require signaling along the MAPK pathway and, more specifically, the presence of the functional BRAF kinase. all breakpoints in the RET gene occur within intron 11, leaving intact the TK domain of the receptor and enabling the RET/PTC oncoprotein to bind SHC via Y1062 and activate the RAS-RAF-MAPK cascade |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Thyroid cancer |
| + |
TEK | up-regulates activity
binding
|
SHC1 |
0.57 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-242573 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 14665640 |
Our results identified a novel interaction between Tie2 with the adapter molecule ShcA and suggested that this interaction may play a role in the regulation of migration and three-dimensional organization of endothelial cells induced by angiopoietin-1. Furthermore, Tyr-1101 of Tie2 was identified as the primary binding site for the SH2 domain of ShcA. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
IL2RB | up-regulates
binding
|
SHC1 |
0.548 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-204975 |
|
|
Homo sapiens |
T-lymphocyte, Leukemia Cell, Lymphoma Cell |
| pmid |
sentence |
| 24737791 |
The signaling mechanism utilizes an adaptor protein, shc, which binds to a phosphotyrosine residue on the il-2/15r?, Resulting in activation of grb2 and onto akt via the shc-grb2-gab2-pi3k-akt signaling pathway to increase cell proliferation and/or survival |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
LTK | up-regulates
phosphorylation
|
SHC1 |
0.425 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-49625 |
|
|
Homo sapiens |
Neuron |
| pmid |
sentence |
| 9223670 |
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. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SHC1 | up-regulates activity
|
MAPK1 |
0.711 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-242622 |
|
|
Mus musculus |
NIH-3T3 Cell |
| pmid |
sentence |
| 17673906 |
We report that upon TGF__ stimulation, the activated TGF__ type I receptor (T_RI) recruits and directly phosphorylates ShcA proteins on tyrosine and serine. This dual phosphorylation results from an intrinsic T_RI tyrosine kinase activity that complements its well_defined serine_threonine kinase function. TGF___induced ShcA phosphorylation induces ShcA association with Grb2 and Sos, thereby initiating the well_characterised pathway linking receptor tyrosine kinases with Erk MAP kinases. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
SHC1 | up-regulates activity
|
ERK1/2 |
0.718 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-242628 |
|
|
Mus musculus |
NIH-3T3 Cell |
| pmid |
sentence |
| 17673906 |
We report that upon TGF__ stimulation, the activated TGF__ type I receptor (T_RI) recruits and directly phosphorylates ShcA proteins on tyrosine and serine. This dual phosphorylation results from an intrinsic T_RI tyrosine kinase activity that complements its well_defined serine_threonine kinase function. TGF___induced ShcA phosphorylation induces ShcA association with Grb2 and Sos, thereby initiating the well_characterised pathway linking receptor tyrosine kinases with Erk MAP kinases. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, EGFR Signaling, FLT3-ITD in AML, IL6 Signaling, Noonan syndrome, Thyroid cancer |
| + |
RET | up-regulates
binding
|
SHC1 |
0.65 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-36902 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 8183561 |
We have shown that the sh2 domain of the adaptor protein shc coimmunoprecipitates with all the ret. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Thyroid cancer |
| + |
IL6ST | up-regulates
binding
|
SHC1 |
0.345 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250574 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9126968 |
Shc mediates IL-6 signaling by interacting with gp130 and Jak2 kinase. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | IL6 Signaling |
4.0
SHC1
- 
- 