Thrombin-induced inhibition of myoblast differentiation is mediated by Gbetagamma.
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 G(12), we examined which subunits of heterotrimeric guanine nucleotide-binding regulatory proteins (Galpha(i), Galpha(q/11), Galpha(12) or Gbetagamma) participate in the thrombin-induced inhibition of C2C12 myoblast differentiation. Galpha(i2) and Galpha(11) had no inhibitory effect on the myogenic differentiation. Galpha(12) prevented only myoblast fusion, whereas Gbetagamma 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 beta-adrenergic receptor kinase, which is known to sequester free Gbetagamma. These results suggest that the thrombin-induced inhibition of muscle differentiation is mainly mediated by Gbetagamma.
Nagao
M
M
Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, Japan.
Kaziro
Y
Y
Itoh
H
H
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D013917:Thrombin / Q000378:metabolism* / Q000494:pharmacology
C118981:G-protein Beta gamma; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D011518:Proto-Oncogene Proteins; D013917:Thrombin; D019204:GTP-Binding Proteins; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; C498016:Gnai2 protein, mouse; C498017:Gnai2 protein, rat; D020962:Heterotrimeric GTP-Binding Proteins