Reactome | GAB1 binds PTPN11

GAB1 binds PTPN11

Stable Identifier

R-HSA-8865994

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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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
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
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
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