Thrombin‐induced inhibition of myoblast differentiation is mediated by Gβγ

FEBS Letters

Itoh, Hiroshi¹  Kaziro, Yoshito¹  Nagao, Motoshi¹ 

[1]Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan

关键词: Thrombin;    G protein;    Gβγ;    Myoblast differentiation;    Gα12;    Myotube formation;    bHLH;    basic helix-loop-helix;    MHC;    myosin heavy chain;    FGF;    fibroblast growth factor;    G protein;    heterotrimeric guanine nucleotide-binding regulatory protein;    GM;    growth medium;    DM;    differentiation medium;    Csk;    C-terminal Src kinase;   

DOI  :  10.1016/S0014-5793(00)01458-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Thrombin has been shown to inhibit skeletal muscle differentiation. However, the mechanisms by which thrombin represses myogenesis remain unknown. Since the thrombin receptor couples to G_i, G_q/11 and G₁₂, we examined which subunits of heterotrimeric guanine nucleotide-binding regulatory proteins (Gα_i, Gα_q/11, Gα₁₂ or Gβγ) participate in the thrombin-induced inhibition of C2C12 myoblast differentiation. Gα_i2 and Gα₁₁ had no inhibitory effect on the myogenic differentiation. Gα₁₂ prevented only myoblast fusion, whereas Gβγ inhibited both the induction of skeletal muscle-specific markers and the myotube formation. In addition, the thrombin-induced reduction of creatine kinase activity was blocked by the C-terminal peptide of β-adrenergic receptor kinase, which is known to sequester free Gβγ. These results suggest that the thrombin-induced inhibition of muscle differentiation is mainly mediated by Gβγ.

【 授权许可】

Unknown