Negative Regulation of the RalGAP Complex by 14-3-3 |
| |
| Authors: | Dara Leto Maeran Uhm Anja Williams Xiao-wei Chen Alan R. Saltiel |
| |
| Affiliation: | From the ‡Life Sciences Institute.;§Department of Molecular and Integrative Physiology, and ;¶Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109 |
| |
| Abstract: | RGC1 and RGC2 comprise a functional RalGAP complex (RGC) that suppresses RalA activity. The PI3-kinase/Akt signaling pathway activates RalA through phosphorylation-mediated inhibition of the RGC. Here we identify a novel phosphorylation-dependent interaction between 14-3-3 and the RGC. 14-3-3 binds to the complex through an Akt-phosphorylated residue, threonine 715, on RGC2. Interaction with 14-3-3 does not alter in vitro activity of the GTPase-activating protein complex. However, blocking the interaction between 14-3-3 and RGC2 in cells increases suppression of RalA activity by the RGC, suggesting that 14-3-3 inhibits the complex through a non-catalytic mechanism. Together, these data show that 14-3-3 negatively regulates the RGC downstream of the PI3-kinase/Akt signaling pathway. |
| |
| Keywords: | Adipocyte Akt G Proteins GTPase Insulin 14-3-3 GTPase-activating Protein (GAP) |
|
|
