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Published on: February 12, 2020
Suppression of c-Src activity stimulates muscle differentiation via p38 MAPK activation
Min Jin Lim1, Yong Hak Seo, Kyu Jin Choi
1Department 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.
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.
Insights
Suppression of c-Src kinase activity promotes muscle differentiation by activating p38 MAPK. This study clarifies the role of c-Src in myogenesis using cell line models.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The role of c-Src (a non-receptor tyrosine kinase) in muscle differentiation is complex and debated.
- Understanding c-Src's precise function is crucial for elucidating mechanisms of myogenesis.
Purpose of the Study:
- To investigate whether c-Src positively or negatively regulates muscle differentiation.
- To determine the signaling pathways modulated by c-Src during myogenesis.
Main Methods:
- Utilized H9c2 and C2C12 cell lines for muscle differentiation studies.
- Employed pharmacologic inhibitors (PP1, SU6656) and dominant-negative c-Src expression to inhibit c-Src activity.
- Analyzed the Raf/MEK/ERK and p38 MAPK signaling pathways.
Main Results:
- Inhibition of c-Src induced muscle differentiation in proliferation medium.
- c-Src activity decreased during differentiation; its inhibition suppressed Raf/MEK/ERK but activated p38 MAPK.
- Concomitant inhibition of c-Src and p38 MAPK blocked differentiation.
Conclusions:
- Suppression of c-Src activity stimulates muscle differentiation.
- This stimulation is mediated, at least in part, by the activation of p38 MAPK.
- c-Src acts as a negative regulator of muscle differentiation through the Raf/MEK/ERK pathway and its suppression allows p38 MAPK activation.
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