Proposed mechanism for Src activation by the G-CSFR through the recruitment of the tyrosine phosphatase Shp2 via the scaffolding protein Gab2. (A) Before engagement of the G-CSFR by ligand, Gab2 associates with phosphor Lyn Tyr507 through Gab2's polyproline motif interacting with Lyn's SH3 domain. Gab2 also interacts with an adaptor protein Grb2. (B) After G-CSF stimulation, tyrosine kinases such as Jak2 can phosphorylate the G-CSFR at sites such as Tyr764. The SH2 domain of Grb2 binds the G-CSFR, bringing the Gab2-Lyn complex to the receptor. (C) A tyrosyl phosphorylated form of Gab2 can then recruit Shp2 via the SH2 domain. (D) Shp2 can then dephosphorylate phosphor Lyn Tyr507, leading to Lyn's activation and autophosphorylation at the positive regulatory site Tyr396 (not shown).