GAB1 binds PTPN11

Stable Identifier
R-HSA-8865994
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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Phosphorylated tyrosine residues Y627 and Y659 of GAB1 serve as docking sites for the N-terminal and C-terminal SH2 domains of PTNP11 (SHP2), respectively, thus recruiting PTNP11 to the activated MET receptor (Schaeper et al. 2000, Cunnick et al. 2001). During mouse embryonic development, Gab1-mediated recruitment of Ptpn11 is crucial for Met receptor-directed placental development and migration of muscle progenitor cells to the limbs (Schaeper et al. 2007). PTPN11 is phosphorylated in response to HGF treatment, although phosphorylation sites and direct MET involvement have not been examined (Duan et al. 2006). Phosphorylation of PTPN11 at tyrosine residues Y542 and Y580 of splicing isoform 2 (matching Y546 and Y584 of PTPN11 splicing isoform 1) is required for PTPN11 phosphatase activity and for the recruitment of downstream effectors, such as GRB2 (Lu et al. 2001). Phosphorylation of PTPN11 in response to HGF treatment is required for the recruitment and activation of sphingosine kinase SPHK1, which may play a role in HGF-induced cell scattering (Duan et al. 2006). While PTPN11 promotes MAPK3/1 (ERK1/2) signaling downstream of MET, it can also dephosphorylate MET on unidentified tyrosine residues (Furcht et al. 2014).

Literature References
PubMed ID Title Journal Year
11323411 Phosphotyrosines 627 and 659 of Gab1 constitute a bisphosphoryl tyrosine-based activation motif (BTAM) conferring binding and activation of SHP2

Cunnick, JM, Mei, L, Doupnik, CA, Wu, J

J Biol Chem 2001
10871282 Coupling of Gab1 to c-Met, Grb2, and Shp2 mediates biological responses

Schaeper, U, Gehring, NH, Fuchs, KP, Sachs, M, Kempkes, B, Birchmeier, W

J. Cell Biol. 2000
17881575 Distinct requirements for Gab1 in Met and EGF receptor signaling in vivo

Schaeper, U, Vogel, R, Chmielowiec, J, Huelsken, J, Rosario, M, Birchmeier, W

Proc. Natl. Acad. Sci. U.S.A. 2007
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