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.
| Original language | English |
|---|---|
| Pages (from-to) | 401-415 |
| Number of pages | 15 |
| Journal | Experimental Cell Research |
| Volume | 252 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 1999 Nov 1 |
| Externally published | Yes |
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- Cell Biology
Cite this
Promotion of skeletal muscle differentiation by K252a with tyrosine phosphorylation of focal adhesion : A possible involvement of small GTPase Rho. / Lee, Kun Ho; Lee, Seung Hye; Kim, Daegun; Rhee, Sangmyung; Kim, Chungho; Chung, Chin Ha; Kwon, Hyockman; Kang, Man Sik.
In: Experimental Cell Research, Vol. 252, No. 2, 01.11.1999, p. 401-415.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Promotion of skeletal muscle differentiation by K252a with tyrosine phosphorylation of focal adhesion
T2 - A possible involvement of small GTPase Rho
AU - Lee, Kun Ho
AU - Lee, Seung Hye
AU - Kim, Daegun
AU - Rhee, Sangmyung
AU - Kim, Chungho
AU - Chung, Chin Ha
AU - Kwon, Hyockman
AU - Kang, Man Sik
PY - 1999/11/1
Y1 - 1999/11/1
N2 - 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.
AB - 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.
KW - Focal adhesion kinase
KW - Focal adhesions
KW - Muscle
KW - P130(Cas)
KW - Paxillin
UR - http://www.scopus.com/inward/record.url?scp=0344240239&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0344240239&partnerID=8YFLogxK
U2 - 10.1006/excr.1999.4648
DO - 10.1006/excr.1999.4648
M3 - Article
C2 - 10527630
AN - SCOPUS:0344240239
VL - 252
SP - 401
EP - 415
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
IS - 2
ER -