Characterization of new regulatory mechanisms and metabolic roles for vav proteins

Résumé

Vav proteins are signal transductors that play bivalent roles as Rho GTPase nucleotide exchange factors and adaptor proteins. In mammals, the family is composed of three members (Vav1, Vav2 and Vav3) that share a distinctive and highly conserved domain structure. These proteins play overlapping but not redundant roles in a wide range of physiological and pathological processes. It is also well known that their regulation is tightly controlled by tyrosine phosphorylation–dependent conformational changes. However, information about other regulatory layers or the contribution of catalytic and adaptor activities to organismal physiology is still lacking. Our findings had led to the identification and characterization of two novel phosphoinositide– and lysine acetylation–mediated regulatory mechanisms for Vav1 in T cells. In addition, we have unveiled a new catalysis–dependent role of Vav2 in IGF-1 and insulin signaling in skeletal muscle. Altogether, these data expand the current knowledge of Vav proteins in terms of family member– and tissue–specific activation processes. They also shed light into previously unknown functions of Vav2 in skeletal muscle biology and metabolic homeostasis.