Csf3 dimer:2xp-4Y-Csf3r:Lyn:p-Y-Jak1:p-Jak2:p-Syk:p-Hck:p-Tyk2 binds and phosphorylates Shc1, Grb2, Gab2, and Ptpn11

Stable Identifier
R-MMU-9674973
Type
Reaction [omitted]
Species
Mus musculus
Compartment
General
SVG |   | PPTX  | SBGN
Csf3 dimer:2xp-4Y-Csf3r:Lyn:p-Y-Jak1:p-Jak2:p-Syk:p-Hck:p-Tyk2 binds and phosphorylates Shc1, Grb2, Gab2, and Ptpn11

Grb2, Shc, and Ptpn11 bind the cytosolic domain of Csf3r (Gcsfr) (Barge et al. 1996, de Koning et al. 1996, de Koning et al. 1998, Ward et al. 1998, Kendrick et al. 2004) and are phosphorylated (Barge et al. 1996, de Koning et al. 1996, de Koning et al. 1998, Wang et al. 2008, Jack et al. 2009, Zhang et al. 2011). Ptpn11 (SHP2) directly binds the phosphorylated cytosolic domain of Csf3r (Ward et al. 1998)and also appears to bind Csf3r indirectly via phosphorylated Gab2 (Wang et al. 2008, Futami et al. 2011). Lyn is required for phosphorylation of Gab2 (Zhu et al. 2004). The order of binding and phosphorylation is unknown.

Literature References
PubMed ID Title Journal Year
8547634 Specific involvement of tyrosine 764 of human granulocyte colony-stimulating factor receptor in signal transduction mediated by p145/Shc/GRB2 or p90/GRB2 complexes

de Koning, JP, Schelen, AM, Dong, F, van Buitenen, C, Burgering, BM, Bos, JL, Löwenberg, B, Touw, IP

Blood 1996
9824671 Direct binding of Shc, Grb2, SHP-2 and p40 to the murine granulocyte colony-stimulating factor receptor

Ward, AC, Monkhouse, JL, Hamilton, JA, Csar, XF

Biochim. Biophys. Acta 1998
14557262 Contribution of the membrane-distal tyrosine in intracellular signaling by the granulocyte colony-stimulating factor receptor

Kendrick, TS, Lipscombe, RJ, Rausch, O, Nicholson, SE, Layton, JE, Goldie-Cregan, LC, Bogoyevitch, MA

J. Biol. Chem. 2004
21725048 SHP2 tyrosine phosphatase stimulates CEBPA gene expression to mediate cytokine-dependent granulopoiesis

Zhang, L, Friedman, AD

Blood 2011
18644434 G-CSF stimulates Jak2-dependent Gab2 phosphorylation leading to Erk1/2 activation and cell proliferation

Wang, L, Xue, J, Zadorozny, EV, Robinson, LJ

Cell. Signal. 2008
8630373 Tryptophan 650 of human granulocyte colony-stimulating factor (G-CSF) receptor, implicated in the activation of JAK2, is also required for G-CSF-mediated activation of signaling complexes of the p21ras route

Barge, RM, de Koning, JP, Pouwels, K, Dong, F, Löwenberg, B, Touw, IP

Blood 1996
21636860 G-CSF receptor activation of the Src kinase Lyn is mediated by Gab2 recruitment of the Shp2 phosphatase

Futami, M, Zhu, QS, Whichard, ZL, Xia, L, Ke, Y, Neel, BG, Feng, GS, Corey, SJ

Blood 2011
14656892 G-CSF-induced tyrosine phosphorylation of Gab2 is Lyn kinase dependent and associated with enhanced Akt and differentiative, not proliferative, responses

Zhu, QS, Robinson, LJ, Roginskaya, V, Corey, SJ

Blood 2004
9490675 Proliferation signaling and activation of Shc, p21Ras, and Myc via tyrosine 764 of human granulocyte colony-stimulating factor receptor

de Koning, JP, Soede-Bobok, AA, Schelen, AM, Smith, L, van Leeuwen, D, Santini, V, Burgering, BM, Bos, JL, Löwenberg, B, Touw, IP

Blood 1998
19587381 M-CSF elevates c-Fos and phospho-C/EBPalpha(S21) via ERK whereas G-CSF stimulates SHP2 phosphorylation in marrow progenitors to contribute to myeloid lineage specification

Jack, GD, Zhang, L, Friedman, AD

Blood 2009
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