| First Author | Rodríguez-Fdez S | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 5808 |
| PubMed ID | 33199701 | Mgi Jnum | J:297811 |
| Mgi Id | MGI:6479291 | Doi | 10.1038/s41467-020-19489-z |
| Citation | Rodriguez-Fdez S, et al. (2020) Vav2 catalysis-dependent pathways contribute to skeletal muscle growth and metabolic homeostasis. Nat Commun 11(1):5808 |
| abstractText | Skeletal muscle promotes metabolic balance by regulating glucose uptake and the stimulation of multiple interorgan crosstalk. We show here that the catalytic activity of Vav2, a Rho GTPase activator, modulates the signaling output of the IGF1- and insulin-stimulated phosphatidylinositol 3-kinase pathway in that tissue. Consistent with this, mice bearing a Vav2 protein with decreased catalytic activity exhibit reduced muscle mass, lack of proper insulin responsiveness and, at much later times, a metabolic syndrome-like condition. Conversely, mice expressing a catalytically hyperactive Vav2 develop muscle hypertrophy and increased insulin responsiveness. Of note, while hypoactive Vav2 predisposes to, hyperactive Vav2 protects against high fat diet-induced metabolic imbalance. These data unveil a regulatory layer affecting the signaling output of insulin family factors in muscle. |
