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Promotion of Skeletal Muscle Differentiation by K252a With Tyrosine Phosphorylation of Focal Adhesion: A Possible Involvement of Small GTPase Rho

K H Lee, S H Lee, D Kim, S Rhee, C Kim, C H Chung, H Kwon, M S Kang

Exp Cell Res. 1999 Nov 1;252(2):401-15.

PMID: 10527630

Abstract:

K252a, a protein kinase inhibitor, acts as a neurotrophic factor in several neuronal cells. In this study we show that K252a enhanced the differentiation of C2C12 myoblasts as well as tyrosine phosphorylation of several focal adhesion-associated proteins including p130(Cas), focal adhesion kinase, and paxillin. The tyrosine phosphorylation of these proteins, reaching a maximum at 30 min after K252a treatment, closely correlated with the colocalization of these proteins in focal adhesion complexes and the coimmunoprecipitation of these proteins with p130(Cas). In addition, K252a stimulated longitudinal development of stress fiber-like structures and cell-matrix interaction in postmitotic myoblasts and eventually formation of well-developed myofibrils in multinucleated myotubes. Herbimycin A, a potent inhibitor of Src family kinases, and cytochalasin D, a selective disrupting-agent of actin filament, completely inhibited K252a-induced tyrosine phosphorylation as well as myoblast differentiation. Similar inhibitory effect was observed in the cells scrape loaded with a Rho inhibitor, C3 transferase, and the treatment of K252a induced a rapid translocation of Rho. These results are consistent with the model that Rho-dependent tyrosine phosphorylation of focal adhesion-associated proteins plays an important role in skeletal muscle differentiation.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP85753431 K-252c - CAS 85753-43-1 K-252c - CAS 85753-43-1 85753-43-1 Price
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