期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 24, 期 3, 页码 1245-1255出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.24.3.1245-1255.2004
关键词
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In this work, we report the implication of the pleckstrin homology (PH) domain-containing protein CKIP-1 in phosphatidytinositol 3-kinase (PI3-K) -regulated muscle differentiation. CKIP-1 is upregulated during muscle differentiation in C2C12 cells. We show that CKIP-1 binds to phosphatidylinositol 3-phosphate through its PH domain and localizes to the plasma membrane in a P13-K-dependent manner. Activation of P13-K by insulin or expression of an active form of P13-K p110 induces a rapid translocation of CKIP-1 to the plasma membrane. Conversely, expression of the 3-phosphoinositide phosphatase myotubularin or P13-K inhibition by LY294002, wortmannin, or mutant p85 abolishes CKIP-1 binding to the membrane. Upon induction of differentiation in low-serum medium, CKIP-1 overexpression in C2C12 myoblasts first promotes proliferation and then stimulates the expression of myogenin and cell fusion in a manner reminiscent of the dual positive effect of insulin-like growth factors on muscle cells. Interference with the P13-K pathway impedes the effect of CKIP-1 on C2C12 cell differentiation. Finally, silencing of CKIP-1 by RNA interference abolishes proliferation and delays myogenin expression. Altogether, these data strongly implicate CKIP-1 as a new component of P13-K signaling in muscle differentiation.
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