4/ Through extensive signaling and cell biology experiments (including developing a SHP2 pY62 antibody in collaboration with
@CellSignal), we delineate an RTK–SFK–SHP2–MAPK signaling axis. Initially we assumed RTKs themselves phosphorylated Y62, but this was not the case. Analysis using
@KinaseLibrary developed by
@CantleyLab instead pointed to SRC family kinases (SFKs). Using pharmacologic and genetic approaches we confirmed that SFKs drive SHP2 phosphorylation downstream of RTKs. A key experiment used SFK KO MEFs developed by Philippe Soriano, where SHP2 phosphorylation was essentially abolished, including Y62 as well as the canonical Y542/Y580 sites.