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.
de Oliveira
Michel V
MV
Department of Internal Medicine, School of Medicine State University of Campinas, Brazil.
Marin
Talita M
TM
Clemente
Carolina F
CF
Costa
Ana Paula Dalla
AP
Judice
Carla C
CC
Franchini
Kleber G
KG
D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D002478:Cells, Cultured; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D051379:Mice; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000166:cytology; D032446:Myoblasts / Q000166:cytology; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000502:physiology*; D015398:Signal Transduction; D015854:Up-Regulation
D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; C516725:Ptpn11 protein, mouse