About the FRS-mediated FGFR4 signaling pathway
The FRS family of scaffolding adaptor proteins has two members, FRS2 (also known as FRS2 alpha) and FRS3 (also known as FRS2beta or SNT-2). Activation of FGFR tyrosine kinase allows FRS proteins to become phosphorylated on tyrosine residues and then bind to the adaptor GRB2 and the tyrosine phosphatase PPTN11/SHP2. Subsequently, PPTN11 activates the RAS-MAP kinase pathway and GRB2 activates the RAS-MAP kinase , PI-3-kinase and ubiquitinations/degradation pathways by binding to SOS, GAB1 and CBL, respectively, via the SH3 domains of GRB2. FRS2 acts as a central mediator in FGF signaling mainly because it induces sustained levels of activation of ERK with ubiquitous expression.
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Gene Symbol | Full Name |
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ACTN2 | actinin, alpha 2 |
ANGPT1 | angiopoietin 1 |
ARAF | A-Raf proto-oncogene, serine/threonine kinase |
ARRB1 | arrestin, beta 1 |
ARRB2 | arrestin, beta 2 |
BRAF | B-Raf proto-oncogene, serine/threonine kinase |
BTC | betacellulin |
CALM1 | calmodulin 1 (phosphorylase kinase, delta) |
CALM2 | calmodulin 2 (phosphorylase kinase, delta) |
CALM3 | calmodulin 3 (phosphorylase kinase, delta) |
CAMK2A | calcium/calmodulin-dependent protein kinase II alpha |
CAMK2B | calcium/calmodulin-dependent protein kinase II beta |
CAMK2D | calcium/calmodulin-dependent protein kinase II delta |
CAMK2G | calcium/calmodulin-dependent protein kinase II gamma |
CSF2 | colony stimulating factor 2 (granulocyte-macrophage) |
CSF2RA | colony stimulating factor 2 receptor, alpha, low-affinity (granulocyte-macrophage) |
CSF2RB | colony stimulating factor 2 receptor, beta, low-affinity (granulocyte-macrophage) |
CSK | c-src tyrosine kinase |
DLG4 | discs, large homolog 4 (Drosophila) |
HBEGF | heparin-binding EGF-like growth factor |
DUSP1 | dual specificity phosphatase 1 |
DUSP2 | dual specificity phosphatase 2 |
DUSP4 | dual specificity phosphatase 4 |
DUSP5 | dual specificity phosphatase 5 |
DUSP6 | dual specificity phosphatase 6 |
DUSP7 | dual specificity phosphatase 7 |
DUSP8 | dual specificity phosphatase 8 |
DUSP9 | dual specificity phosphatase 9 |
EGF | epidermal growth factor |
EGFR | epidermal growth factor receptor |
ERBB2 | erb-b2 receptor tyrosine kinase 2 |
ERBB3 | erb-b2 receptor tyrosine kinase 3 |
ERBB4 | erb-b2 receptor tyrosine kinase 4 |
EREG | epiregulin |
FGA | fibrinogen alpha chain |
FGB | fibrinogen beta chain |
FGF1 | fibroblast growth factor 1 (acidic) |
FGF2 | fibroblast growth factor 2 (basic) |
FGF3 | fibroblast growth factor 3 |
FGF4 | fibroblast growth factor 4 |
FGF5 | fibroblast growth factor 5 |
FGF6 | fibroblast growth factor 6 |
FGF7 | fibroblast growth factor 7 |
FGF8 | fibroblast growth factor 8 (androgen-induced) |
FGF9 | fibroblast growth factor 9 |
FGF10 | fibroblast growth factor 10 |
FGFR1 | fibroblast growth factor receptor 1 |
FGFR3 | fibroblast growth factor receptor 3 |
FGFR2 | fibroblast growth factor receptor 2 |
FGFR4 | fibroblast growth factor receptor 4 |
FGG | fibrinogen gamma chain |
FN1 | fibronectin 1 |
FYN | FYN proto-oncogene, Src family tyrosine kinase |
GRB2 | growth factor receptor-bound protein 2 |
GRIN1 | glutamate receptor, ionotropic, N-methyl D-aspartate 1 |
GRIN2A | glutamate receptor, ionotropic, N-methyl D-aspartate 2A |
GRIN2B | glutamate receptor, ionotropic, N-methyl D-aspartate 2B |
GRIN2C | glutamate receptor, ionotropic, N-methyl D-aspartate 2C |
GRIN2D | glutamate receptor, ionotropic, N-methyl D-aspartate 2D |
NRG1 | neuregulin 1 |
HRAS | Harvey rat sarcoma viral oncogene homolog |
IL2 | interleukin 2 |
IL2RA | interleukin 2 receptor, alpha |
IL2RB | interleukin 2 receptor, beta |
IL2RG | interleukin 2 receptor, gamma |
IL3 | interleukin 3 |
IL3RA | interleukin 3 receptor, alpha (low affinity) |
IL5 | interleukin 5 |
IL5RA | interleukin 5 receptor, alpha |
IRS1 | insulin receptor substrate 1 |
ITGA2B | integrin, alpha 2b (platelet glycoprotein IIb of IIb/IIIa complex, antigen CD41) |
ITGB3 | integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61) |
JAK1 | Janus kinase 1 |
JAK2 | Janus kinase 2 |
JAK3 | Janus kinase 3 |
KIT | v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog |
KRAS | Kirsten rat sarcoma viral oncogene homolog |
MARK3 | MAP/microtubule affinity-regulating kinase 3 |
KITLG | KIT ligand |
MAP3K11 | mitogen-activated protein kinase kinase kinase 11 |
NCAM1 | neural cell adhesion molecule 1 |
NEFL | neurofilament, light polypeptide |
NF1 | neurofibromin 1 |
NRAS | neuroblastoma RAS viral (v-ras) oncogene homolog |
PEBP1 | phosphatidylethanolamine binding protein 1 |
PDGFA | platelet-derived growth factor alpha polypeptide |
PDGFB | platelet-derived growth factor beta polypeptide |
PDGFRA | platelet-derived growth factor receptor, alpha polypeptide |
PDGFRB | platelet-derived growth factor receptor, beta polypeptide |
PHB | prohibitin |
PPP2CA | protein phosphatase 2, catalytic subunit, alpha isozyme |
PPP2CB | protein phosphatase 2, catalytic subunit, beta isozyme |
PPP2R1A | protein phosphatase 2, regulatory subunit A, alpha |
PPP2R1B | protein phosphatase 2, regulatory subunit A, beta |
PPP2R5A | protein phosphatase 2, regulatory subunit B', alpha |
PPP2R5B | protein phosphatase 2, regulatory subunit B', beta |
PPP2R5C | protein phosphatase 2, regulatory subunit B', gamma |
PPP2R5D | protein phosphatase 2, regulatory subunit B', delta |
PPP2R5E | protein phosphatase 2, regulatory subunit B', epsilon isoform |
PPP5C | protein phosphatase 5, catalytic subunit |