title: Suppression of c-Src activity stimulates muscle differentiation via p38 MAPK activation.
abstract: Role of c-Src in muscle differentiation has been controversial. Here, we investigated if c-Src positively or negatively regulates muscle differentiation, using H9c2 and C2C12 cell lines. Inhibition of c-Src by treatment with PP1 and SU6656, pharmacologic inhibitors of Src family kinases, or by expression of a dominant negative c-Src, all induced muscle differentiation in proliferation medium (PM). In differentiating cells in differentiation medium (DM), c-Src activity gradually decreased and reached basal level 3 days after induction of differentiation. Inhibition of c-Src suppressed Raf/MEK/ERK pathway but activated p38 MAPK. Inhibition of p38 MAPK did not affect c-Src activity in PM. However, it reactivated Raf/MEK/ERK pathway in c-Src-inhibited cells regardless of PM or DM. Concomitant inhibition of c-Src and p38 MAPK activities blocked muscle differentiation in both media. In conclusion, suppression of c-Src activity stimulates muscle differentiation by activating p38 MAPK uni-directionally.
authors.affiliation: Department of Biochemistry and Molecular Biology (BK21 project), Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Min Jin
authors.initials: MJ
authors.lastname: Lim
authors.forename: Yong Hak
authors.initials: YH
authors.lastname: Seo
authors.forename: Kyu Jin
authors.initials: KJ
authors.lastname: Choi
authors.forename: Chang Hoon
authors.initials: CH
authors.lastname: Cho
authors.forename: Bum Shik
authors.initials: BS
authors.lastname: Kim
authors.forename: Yun Hong
authors.initials: YH
authors.lastname: Kim
authors.forename: Jinhwa
authors.initials: J
authors.lastname: Lee
authors.forename: Hansoo
authors.initials: H
authors.lastname: Lee
authors.forename: Chan Y
authors.initials: CY
authors.lastname: Jung
authors.forename: Joohun
authors.initials: J
authors.lastname: Ha
authors.forename: Insug
authors.initials: I
authors.lastname: Kang
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Kim
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D016391:Genes, src / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D011505:Protein-Tyrosine Kinases; D048051:p38 Mitogen-Activated Protein Kinases