Skeletal muscle myogenesis is regulated by G protein-coupled receptor kinase 2, GRK2

Abstract

Resumen del póster presentado al XXXIV Congreso de la Sociedad Española de Bioquímica y Biología Molecular, celebrado en Barcelona del 5 al 8 de septiembre de 2011.GRK2 is the more ubiquitous G protein-coupled receptor kinase isoform and, additionally to its role in GPCR desensitization, it has been implicated in the modulation of different intracellular signalling pathways. Recently, GRK2 has been identified as a novel inactivating kinase of p38MAPK that interferes with 3T3L1 differentiation. Therefore, a possible role for GRK2 in the differentiation of myocytic cells remains to be explored. In this regard, the main objective was to investigate the contribution of GRK2 to myogenesis.We analyzed myoblast C2C12 differentiation and cell cycle protein expression. In this issue we generated stable cell lines that overexpressed wild-type GRK2 or GRK2 catalytically-deficient mutant (K220R). Overexpression of wild-type GRK2 impaired the myoblast fusion and the expression of myogenic markers. These cells were unable to activate not only p38MAPK but also Akt pathways. However, cells overexpressing GRK2 kinasedeficient mutant differentiated in the same way as wild-type cells. We also analyzed the skeletal muscle phenotypic and functional differences between Wt and GRK2 hemizygous animals. GRK2+/- mice exhibited increased muscle fibber size and less number of fibbers compared to Wt animals. Furthermore, we also observed that this hypertrophy is consistent with increased glucose clearance into skeletal muscle in 9-month-old GRK2+/- mice, suggesting that the muscle of these animals preserved its functionality better than Wt mice during the elderly. We conclude that GRK2 inactivation leads to increased Akt and p38MAPK signalling improving skeletal muscle differentiation. Our data identify GRK2 as a negative regulator of skeletal muscle myogenesis, which uncovers an important new function in the signalling networks of this protein.Peer reviewe