Lysine Acetylation Reshapes The Downstream Signaling Landscape Of Vav1 In Lymphocytes

Abstract

Vav1 works both as a catalytic Rho GTPase activator and an adaptor molecule. These functions, which are critical for T cell development and antigenic responses, are tyrosine phosphorylation-dependent. However, it is not known whether other posttranslational modifications can modulate the signaling output of this protein. Here, we show that Vav1 becomes acetylated in a stimulation- and SH2 domain-dependent manner. We also demonstrate that the acetylation of four residues located in the catalytic, lysine rich and SH2 domains preferentially buffers the Vav1 adaptor function that favors the stimulation of the nuclear factor of activated T cells. As a result, it modifies the signaling diversification properties normally exhibited by Vav1 in lymphocytes. This new regulatory layer is not shared by Vav family paralogs.