THE PH DOMAIN OF RAS-GAP IS SUFFICIENT FOR IN-VITRO BINDING TO BETA-GAMMA-SUBUNITS OF HETEROTRIMERIC G-PROTEINS

1. The noncatalytic domain of Ras-GAP can affect signaling through G p rotein-coupled receptors by a poorly understood mechanism. 2. In this study, fusion proteins containing elements of the noncatalytic domain of ras-GAP were examined for their ability to bind beta gamma subunits of heterotrimeric G proteins and phosphotyrosine-containing polypepti des. 3. Our results demonstrate that purified beta gamma dimers associ ated with bacterially expressed GAP proteins and that this association does not require SH2 or SH3 domains but is dependent on the presence of the GAP pleckstrin-homology (PH) domain. In contrast, only the SH2 domains are necessary for binding to tyrosine phosphorylated proteins. 4. These findings raise the possibility that heterotrimeric G protein s might affect functioning of ras-like proteins through beta gamma sub units acting on their regulatory molecules.