Promotion of skeletal muscle differentiation by K252a with tyrosine
phosphorylation of focal adhesion: a possible involvement of small GTPase Rho.
Lee KH, Lee SH, Kim D, Rhee S, Kim C, Chung CH, Kwon H, Kang MS.
Department of Molecular Biology, Research Center for Cell Differentiation, Seoul
National University, Seoul, 151-742, Korea.
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. Copyright 1999
Academic Press.
Publication Types:
Research Support, Non-U.S. Gov't
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