|
Lee KH, Lee SH, Kim D, Rhee S, Kim C, Chung CH, Kwon H, Kang MS.
Promotion of skeletal muscle differentiation by K252a with tyrosine
phosphorylation of focal adhesion: a possible involvement of small GTPase Rho.
Exp Cell Res. 1999 Nov 1;252(2):401-15.
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
PMID: 10527630 |
