| + |
ALK |
phosphorylation
|
GRB2 |
0.468 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-247142 |
Tyr160 |
QVPQQPTyVQALFDF |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 20554525 |
Two phosphorylation sites on Grb2 have been identified thus far at position Tyr209 in BCR-ABL-expressing cells (16) and Tyr160 by pp60c-src (18)Previous reports suggested an inhibitory role of Grb2 Tyr7, Tyr37, Tyr52, and Tyr209 phosphorylation in receptor tyrosine kinase signaling (16) (43). Instead, in our system Grb2 Tyr160 mutation was not show to have a role in ALCL proliferation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
BCR-ABL |
phosphorylation
|
GRB2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-247146 |
Tyr160 |
QVPQQPTyVQALFDF |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 20554525 |
Our data show that BCR-ABL also phosphorylates Grb2 in Tyr160Previous reports suggested an inhibitory role of Grb2 Tyr7, Tyr37, Tyr52, and Tyr209 phosphorylation in receptor tyrosine kinase signaling (16) (43). Instead, in our system Grb2 Tyr160 mutation was not show to have a role in ALCL proliferation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, BCR-ABL in AML |
| + |
SRC |
phosphorylation
|
GRB2 |
0.641 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-247138 |
Tyr160 |
QVPQQPTyVQALFDF |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 20554525 |
In our work we show that, in contrast to BCR-ABL and prolactin, NPM-ALK phosphorylates Grb2 mainly in Tyr160)Previous reports suggested an inhibitory role of Grb2 Tyr7, Tyr37, Tyr52, and Tyr209 phosphorylation in receptor tyrosine kinase signaling (16) (43). Instead, in our system Grb2 Tyr160 mutation was not show to have a role in ALCL proliferation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | EGFR Signaling, IL6 Signaling, Integrin Signaling, Rhabdomyosarcoma |
| + |
BCR-ABL | down-regulates activity 
phosphorylation
|
GRB2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-246281 |
Tyr209 |
TGMFPRNyVTPVNRN |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 20554525 |
More recently, however, tyrosine phosphorylation of Grb2 in BCR-ABL-transformed cells on residues Tyr7, Tyr37, Tyr52, and Tyr209 in the SH3 domains has been reported and shown to negatively regulate the Ras/MAPK pathway. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-246289 |
Tyr37 |
EECDQNWyKAELNGK |
Homo sapiens |
|
| pmid |
sentence |
| 20554525 |
More recently, however, tyrosine phosphorylation of Grb2 in BCR-ABL-transformed cells on residues Tyr7, Tyr37, Tyr52, and Tyr209 in the SH3 domains has been reported and shown to negatively regulate the Ras/MAPK pathway. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-246293 |
Tyr52 |
DGFIPKNyIEMKPHP |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 20554525 |
More recently, however, tyrosine phosphorylation of Grb2 in BCR-ABL-transformed cells on residues Tyr7, Tyr37, Tyr52, and Tyr209 in the SH3 domains has been reported and shown to negatively regulate the Ras/MAPK pathway. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-246285 |
Tyr7 |
yDFKATAD |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 20554525 |
More recently, however, tyrosine phosphorylation of Grb2 in BCR-ABL-transformed cells on residues Tyr7, Tyr37, Tyr52, and Tyr209 in the SH3 domains has been reported and shown to negatively regulate the Ras/MAPK pathway. |
|
| Publications: |
4 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, BCR-ABL in AML |
| + |
PTPN11 | up-regulates activity 
dephosphorylation, binding
|
GRB2 |
0.736 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276995 |
Tyr209 |
TGMFPRNyVTPVNRN |
Homo sapiens |
|
| pmid |
sentence |
| 23420874 |
Using an in vitro experiment in which purified full-length wild-type Shp2 (WT Shp2) was incubated with phosphorylated C-SH3 domain of Grb2 we demonstrated that Shp2 can dephosphorylate Grb2 on residue Y209 (XREF_FIG). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263498 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11085989 |
SHP-2 is thus a positive regulator of ERK by leptin receptors, and both the adaptor function and the phosphatase activity of SHP-2 are critical for this regulation. Based on these data, we conclude that tyrosinephosphorylation of SHP-2 is a mediator of ERK activation viaTyr-985. This is likely to occur via Grb-2 binding to SHP-2 atthe C terminus followed by activation of the Ras-Raf pathwayas suggested for other signaling systems (55, 56) and morerecently for the leptin receptor (33). |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, FLT3 in AML, KIT in AML, EGFR Signaling, Noonan syndrome |
| + |
BCR-ABL | down-regulates
phosphorylation
|
GRB2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-112354 |
Tyr209 |
TGMFPRNyVTPVNRN |
Homo sapiens |
A-431 Cell |
| pmid |
sentence |
| 11726515 |
Phosphorylation of grb2 by bcr/abl or egf receptor reduced its sh3-dependent binding to sos in vivo, but not its sh2-dependent binding to bcr/abl. Tyr209 within the c-terminal sh3 domain of grb2 was identified as one of the tyrosine phosphorylation sites |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, BCR-ABL in AML |
| + |
EGFR |
phosphorylation
|
GRB2 |
0.924 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235738 |
Tyr209 |
TGMFPRNyVTPVNRN |
Homo sapiens |
A-431 Cell |
| pmid |
sentence |
| 11726515 |
Phosphorylation of grb2 by bcr/abl or egf receptor reduced its sh3-dependent binding to sos in vivo, but not its sh2-dependent binding to bcr/abl. Tyr209 within the c-terminal sh3 domain of grb2 was identified as one of the tyrosine phosphorylation sites |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, COVID-19 Causal Network, EGFR Signaling, Glioblastoma Multiforme, Hepatocellular Tumor, Noonan syndrome, Non-small-cell lung cancer (NSCLC), PI3K/AKT Signaling, SARS-CoV MAPK PERTURBATION |
| + |
GRB2 | down-regulates 
|
KIT |
0.648 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-157956 |
|
|
Homo sapiens |
Leukemia Cell |
| pmid |
sentence |
| 17904548 |
Grb2 mediates c-kit degradation through recruitment of cbl to c-kit, leading to ubiquitination of c-kit followed by internalization and degradation |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, KIT in AML, Malignant Melanoma |
| + |
MET | up-regulates activity
binding
|
GRB2 |
0.694 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256261 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22128289 |
For activation of the mitogen-activated protein kinase (MAPK) cascades, c-MET activation stimulates the activity of the rat sarcoma viral oncogene homolog (RAS) guanine nucleotide exchanger son of sevenless (SOS) via binding with SHC and GRB2 leading to the activation of RAS. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Hepatocellular Tumor, Rhabdomyosarcoma |
| + |
LAT | up-regulates
binding
|
GRB2 |
0.804 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251520 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23150273 |
Phosphorylated tyrosines 171, 191, and 226 [in LAT] bind to the SH2 domains of the Grb2 family of adaptor proteins and must be present for optimal signalling |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251521 |
|
|
Homo sapiens |
JURKAT Cell |
| pmid |
sentence |
| 10811803 |
Our results showed that three distal tyrosines, Tyr(171), Tyr(191), and Tyr(226), are responsible for Grb2-binding; |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | B-cell activation, T cell activation |
| + |
GRB2 | up-regulates activity
relocalization
|
SOS1 |
0.913 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236792 |
|
|
Homo sapiens |
U-937 Cell |
| pmid |
sentence |
| 10570290 |
Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-39163 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 8479541 |
Furthermore, our results indicate that the interaction domains of sos1 and grb2 have evolved so as to bind ligands not with maximal strength but with specificities and affinities that maintain cooperativity. Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235773 |
|
|
Mus musculus |
Embryonic Cell Line |
| pmid |
sentence |
| 23452850 |
Interaction domains of sos1/grb2 are finely tuned for cooperative control of embryonic stem cell fate. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens, Mus Musculus |
| Pathways: | Adipogenesis, Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, COVID-19 Causal Network, Colorectal Carcinoma, EGFR Signaling, ErbB receptors in cancer, Glioblastoma Multiforme, Hepatocellular Tumor, IL6 Signaling, Insulin Signaling, Inhibition of Apoptosis, Integrin Signaling, Luminal Breast Cancer, Malignant Melanoma, Noonan syndrome, Non-small-cell lung cancer (NSCLC), PI3K/AKT Signaling, Rett syndrome, Rhabdomyosarcoma, RTKs in cancer, SARS-CoV MAPK PERTURBATION, Thyroid cancer, T cell activation, VEGF Signaling |
| + |
KIT | up-regulates activity
binding
|
GRB2 |
0.648 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248283 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10377264 |
We furthermore demonstrate that the adapter protein Grb2 is a specific binding partner for both phosphorylated Tyr-703 and phosphorylated Tyr-936, whereas the adapter protein Grb7 binds selectively to phosphorylated Tyr-936. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, KIT in AML, Malignant Melanoma |
| + |
BCR-ABL | up-regulates activity
binding
|
GRB2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255820 |
|
|
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 11726515 |
However, direct binding of Grb2 to Bcr/Abl also facilitates its tyrosine phosphorylation, which we propose reflects activation of a physiological negative regulatory mechanism by this oncogenic tyrosine kinase.Direct binding of Grb2 to Bcr/Abl facilitates Grb2 phosphorylation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248199 |
|
|
Chlorocebus aethiops |
COS-7 Cell |
| pmid |
sentence |
| 8402896 |
BCR-ABL-induced oncogenesis is mediated by direct interaction with the SH2 domain of the GRB-2 adaptor protein. Mutation of Y177 to phenylalanine (Y177F) abolishes GRB-2 binding and abrogates BCR-ABL-induced Ras activation |
|
| Publications: |
2 |
Organism: |
Homo Sapiens, Chlorocebus Aethiops |
| Pathways: | Acute Myeloid Leukemia, BCR-ABL in AML |
| + |
CD28 | up-regulates
binding
|
GRB2 |
0.701 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-32509 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 7737275 |
In this study, we demonstrate that the co-stimulatory antigen cd28 binds to grb-2 by means of a cytoplasmic pymnm motif, which is the same motif bound by pi 3-kinase. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-202706 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24098653 |
Binding of the py site in cd28 (py-m-n-m) by pi3k and grb2 through their sh2 domains is a key step that triggers the cd28 signal transduction for t cell activation and differentiation |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | T cell activation |
| + |
GRB2 | up-regulates
binding
|
ABL1 |
0.578 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-39049 |
|
|
Homo sapiens |
Leukemia Cell |
| pmid |
sentence |
| 8402896 |
We demonstrate that bcr-abl exists in a complex with grb-2 in vivo. Binding of grb-2 to bcr-abl is mediated by the direct interaction of the grb-2 sh2 domain with a phosphorylated tyrosine, y177, within the bcr first exon. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
EGFR | up-regulates activity
binding
|
GRB2 |
0.924 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236327 |
|
|
in vitro |
HeLa Cell |
| pmid |
sentence |
| 16729043 |
We determined interaction partners to all cytosolic tyrosine residues of the four members of the ErbB-receptor family in an unbiased fashion by quantitative proteomics using pull-down experiments with pairs of phosphorylated and nonphosphorylated synthetic peptides. Each receptor had characteristic preferences for interacting proteins and most interaction partners had multiple binding sites on each receptor. EGFR and ErbB4 had several docking sites for Grb2, while ErbB3 was characterized by six binding sites for PI3K. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235721 |
|
|
Mus musculus |
NIH-3T3 Cell |
| pmid |
sentence |
| 7518560 |
Erbb1 recruites grb2 through sh2 domain;from these studies, we concluded that grb2 binds directly to the egfr at y-1068, to a lesser extent at y-1086, and indirectly at y-1173. Egfr has six binding sites for the adapter protein grb2, and erbb4 has five, each with different binding strength several tyrosine-based motifs recruit a number of signal transducers to the phosphorylated form of erbb1 such as the adaptor proteins growth-factor-receptor bound-2 (grb2) and src-homology-2-containing (shc). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267725 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24697349 |
Adaptor protein Grb2 binds phosphotyrosines in the epidermal growth factor (EGF) receptor (EGFR) and thereby links receptor activation to intracellular signaling cascades. |
|
| Publications: |
3 |
Organism: |
In Vitro, Mus Musculus, Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, COVID-19 Causal Network, EGFR Signaling, Glioblastoma Multiforme, Hepatocellular Tumor, Noonan syndrome, Non-small-cell lung cancer (NSCLC), PI3K/AKT Signaling, SARS-CoV MAPK PERTURBATION |
| + |
GCSAM | down-regulates activity
binding
|
GRB2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273608 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 31362927 |
Herein, we demonstrate that the adaptor protein HGAL, specifically expressed in GC lymphocytes and GC-derived lymphomas, directly binds to Grb2 upon BCR activation and negates the inhibitory effects of Grb2 on the BCR-induced biochemical signaling cascade. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SHC1 | up-regulates
binding
|
GRB2 |
0.966 |
| 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-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-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. |
|
| 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. |
|
| Publications: |
4 |
Organism: |
Homo Sapiens, Sus Scrofa, Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, EGFR Signaling, IL6 Signaling, Noonan syndrome, Thyroid cancer |
| + |
SHC3 | up-regulates
relocalization
|
GRB2 |
0.819 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-146897 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16729043 |
In addition to direct binding of grb2 to phosphotyrosine residues of receptor kinases, grb2 can also be recruited to the receptor by binding to shc when shc is tyrosine phosphorylated as a result of receptor stimulation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-147865 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16829981 |
In addition to direct binding of grb2 to phosphotyrosine residues of receptor kinases, grb2 can also be recruited to the receptor by binding to shc when shc is tyrosine phosphorylated as a result of receptor stimulation. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Rett syndrome |
| + |
DOK3 | up-regulates activity
binding
|
GRB2 |
0.556 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268448 |
|
|
Homo sapiens |
B-lymphocyte |
| pmid |
sentence |
| 32323266 |
An adaptor protein Dok-3 mediates the suppressive function of LYN. The Dok-3 phosphorylated by LYN upon BCR stimulation forms a complex with GRB2, which allows it to enter into the signalosome and associate with activation of SHIP protein. This translocation facilitates the efficient inhibition of PLCc2 and SYK from activation, subsequently resulting in the suppression of downstream Ca2+ signaling. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | B-cell activation |
| + |
ERBB4 | up-regulates
binding
|
GRB2 |
0.83 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-146876 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16729043 |
Egfr and erbb4 had several docking sites for grb2, while erbb3 was characterized by six binding sites for pi3k. Egfr has six binding sites for the adapter protein grb2, and erbb4 has five, each with different binding strength. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-147847 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16829981 |
Egfr and erbb4 had several docking sites for grb2, while erbb3 was characterized by six binding sites for pi3k. Egfr has six binding sites for the adapter protein grb2, and erbb4 has five, each with different binding strength. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
CD300LB | up-regulates activity
binding
|
GRB2 |
0.464 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-264833 |
|
|
Chlorocebus aethiops |
COS Cell |
| pmid |
sentence |
| 20959446 |
The CD300b receptor is a non-classical activating receptor able to deliver signals by associating with the transmembrane adaptor protein DAP-12 and the intracellular mediator Grb-2. |
|
| Publications: |
1 |
Organism: |
Chlorocebus Aethiops |
| + |
PDGFRB | up-regulates
binding
|
GRB2 |
0.678 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-34765 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 7935391 |
A pathway leading to activation of the gtp-binding protein ras involves the adaptor molecule grb2. Here we show that tyr-716, a novel autophosphorylation site in the pdgf beta-receptor kinase insert, mediates direct binding of grb2 in vitro and in vivo. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Survival Factors | up-regulates activity 
|
GRB2 |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250559 |
|
|
|
|
| pmid |
sentence |
| 19282669 |
Activation of receptor tyrosine kinases (RTKs) or G protein-coupled receptors (GPCRs) by growth factors or mitogens leads to the recruitment of an adaptor protein Grb2 (growth factor receptor bound protein) and the guanine nucleotide exchange factor (SOS). The SOS activates Ras to recruit and activate Raf at the plasma membrane by phosphorylation at multiple sites. MEK1/2 is which then phosphorylated at two serine residues that subsequently phosphorylates ERK1/2 on both threonine and tyrosine. Activated ERK1/2 phosphorylates RSK and both RSK and ERK translocate to the nucleus where they activates multiple transcription factors ultimately resulting in effector protein synthesis and causing changes in cell proliferation and survival. ERK phosphorylation of MEK and possibly Raf can inactivate the pathway at those steps creating a negative feedback loop. |
|
| Publications: |
1 |
| Pathways: | Inhibition of Apoptosis |
| + |
GRB2 | up-regulates activity
binding
|
INPP5D |
0.581 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268449 |
|
|
Homo sapiens |
B-lymphocyte |
| pmid |
sentence |
| 32323266 |
An adaptor protein Dok-3 mediates the suppressive function of LYN. The Dok-3 phosphorylated by LYN upon BCR stimulation forms a complex with GRB2, which allows it to enter into the signalosome and associate with activation of SHIP protein. This translocation facilitates the efficient inhibition of PLCc2 and SYK from activation, subsequently resulting in the suppression of downstream Ca2+ signaling. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, B-cell activation |
| + |
GRB2 | up-regulates
binding
|
SOS2 |
0.88 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-175180 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21779497 |
Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ERBB2 | up-regulates
relocalization
|
GRB2 |
0.85 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-121968 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 14967450 |
All erbb ligands and receptors couple to activation of the ras-mapk pathway, either directly through sh2 domain-mediated recruitment of grb-2 or indirectly through ptb domain-mediated binding of the shc adaptor |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Colorectal Carcinoma |
| + |
VAV1 | up-regulates
binding
|
GRB2 |
0.685 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-49362 |
|
|
Homo sapiens |
Leukemia Cell |
| pmid |
sentence |
| 9209406 |
Recently, we have shown that the proto-oncogene vav product (vav) is also tyrosine-phosphorylated by treatment with gm-csf and epo and is constitutively associated with the sh3 domain of grb2/ash in ut-7. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
GRB2 | up-regulates
binding
|
GAB2 |
0.912 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-204969 |
|
|
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 |
| + |
ErbB receptor family | up-regulates activity
binding
|
GRB2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256162 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 14967450 |
All erbb ligands and receptors couple to activation of the ras-mapk pathway, either directly through sh2 domain-mediated recruitment of grb-2 or indirectly through ptb domain-mediated binding of the shc adaptor |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | ErbB receptors in cancer, Non-small-cell lung cancer (NSCLC), RTKs in cancer |
| + |
CBLB | up-regulates activity
binding
|
GRB2 |
0.57 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236051 |
|
|
Homo sapiens |
JURKAT Cell |
| pmid |
sentence |
| 8626404 |
Here we show that in unstimulated Jurkat cells Cbl is co-immunoprecipitated with monoclonal antibody against Grb2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, FLT3 in AML, KIT in AML, EGFR Signaling |
| + |
FLT3 | up-regulates activity
binding
|
GRB2 |
0.603 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-245060 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 10080542 |
FL stimulation induces association of Grb2 with Flt3, SHP-2,and Shc |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, FLT3 in AML |
| + |
ERBB3 | up-regulates
binding
|
GRB2 |
0.839 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-121971 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 14967450 |
All erbb ligands and receptors couple to activation of the ras-mapk pathway, either directly through sh2 domain-mediated recruitment of grb-2 or indirectly through ptb domain-mediated binding of the shc adaptor. In this study, we identify grb2 as a specific binding partner to tyrosines y1199 and y1268 of erbb3. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-146858 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16729043 |
All erbb ligands and receptors couple to activation of the ras-mapk pathway, either directly through sh2 domain-mediated recruitment of grb-2 or indirectly through ptb domain-mediated binding of the shc adaptor. In this study, we identify grb2 as a specific binding partner to tyrosines y1199 and y1268 of erbb3. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
IRS1 | up-regulates activity
binding
|
GRB2 |
0.803 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236614 |
|
|
Homo sapiens |
Brown Adipose Tissue |
| pmid |
sentence |
| 11259577 |
Association ofinsulinreceptor substrate 1 (irs-1) y895 with grb-2 mediates theinsulinsignaling involved in irs-1-deficient brown adipocyte mitogenesis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Adipogenesis, Insulin Signaling, Luminal Breast Cancer |
| + |
FGFR2 | up-regulates
phosphorylation
|
GRB2 |
0.772 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-197980 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22726438 |
Inhibition of basal fgf receptor signaling by dimeric grb2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
GRB2 | up-regulates
relocalization
|
CBL |
0.905 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-114704 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11823423 |
The underlying mechanism seems to involve recruitment of a grb2 c-cbl complex to grb2-specific docking sites of egfr, and concurrent acceleration of receptor ubiquitylation and desensitization. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, FLT3 in AML, KIT in AML, Glioblastoma Multiforme |
| + |
KDR | up-regulates activity
relocalization
|
GRB2 |
0.684 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261948 |
|
|
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 |
| Pathways: | VEGF Signaling |
| + |
GRB2 | up-regulates
binding
|
GAB1 |
0.873 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235917 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12766170 |
The gab1 docking protein forms a platform for the assembly of a multiprotein signaling complex downstream from receptor tyrosine kinases. In general, recruitment of gab1 occurs indirectly, via the adapter protein grb2 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | EGFR Signaling, Hepatocellular Tumor, Noonan syndrome, PI3K/AKT Signaling, Rhabdomyosarcoma |
| + |
RTKs | up-regulates activity
binding
|
GRB2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256167 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17306385 |
The adaptor protein Grb2 can bind with activated RTKs through an SH2 domain-phosphotyrosine interaction, while through the SH3 domain (a binding domain specific to proline-rich sequences) Grb2 interacts with the guanine nucleotide exchange factor, Sos. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Integrin Signaling, PI3K/AKT Signaling, RTKs in cancer |
| + |
FRS2 | up-regulates activity
binding
|
GRB2 |
0.802 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236953 |
|
|
Rattus norvegicus |
L-6 Myoblast Cell |
| pmid |
sentence |
| 9182757 |
In this report, we demonstrate that FGF stimulation induces tyrosine phosphorylation of a novel lipid anchored docking protein, termed FRS2, that forms a complex with Grb2/Sos, thus linking FGF-receptor activation to the Ras/MAPK signaling pathway. |
|
| Publications: |
1 |
Organism: |
Rattus Norvegicus |
| Pathways: | Luminal Breast Cancer |
| + |
GRB2 | up-regulates
binding
|
MAP4K1 |
0.455 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-63994 |
|
|
Homo sapiens |
T-lymphocyte |
| pmid |
sentence |
| 9891069 |
The first and second proline-rich motifs containing the grb2 n-sh3-binding consensus sequence (-p-x-x-p-x-r/k-) were implicated in the binding of hpk1 to grb2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | SAPK/JNK Signaling |
| + |
PTK2 | up-regulates activity
binding
|
GRB2 |
0.705 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257733 |
|
|
|
|
| pmid |
sentence |
| 15688067 |
Src-mediated phosphorylation of FAK at Tyr925 creates an SH2 binding site for the growth-factor-receptor-bound protein 2 (GRB2) adaptor protein, which leads to the activation of Ras and the extracellular signal-regulated kinase-2 (ERK2) cascade. |
|
| Publications: |
1 |
| Pathways: | Integrin Signaling, VEGF Signaling |
3.0
GRB2
