SHP-2 regulates myogenesis by coupling to FAK signaling pathway

Transient dephosphorylation of FAK at Tyr-397 is required for cell cycle withdrawal early on during myogenesis. Here, we show that upon serum starvation of C2C12 myoblasts, FAK is transiently dephosphorylated in parallel with SHP-2 activation and association with FAK. SHP-2 knockdown by RNA interference suppressed the transient upregulation of SHP-2 and dephosphorylation of FAK during myogenesis. Furthermore, depletion of SHP-2 retarded the cell cycle withdrawal and the differentiation of serum-starved myoblasts into myotubes. These data provide a mechanistic basis for the reduction in FAK activity in differentiating myoblasts, indicating that myogenesis is critically triggered by FAK/SHP-2 complex.Structured summaryMINT-7258938: Fak1 (uniprotkb:P34152) physically interacts (MI:0915) with shp2 (uniprotkb:P35235) by anti bait coimmunoprecipitation (MI:0006)