Negative Regulation of the RalGAP Complex by 14-3-3

作者：Leto Dara; Uhm Maeran; Williams Anja; Chen Xiao wei; Saltiel Alan R^*

来源：Journal of Biological Chemistry, 2013, 288(13): 9272-9283.

DOI：10.1074/jbc.M112.426106

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.

• 出版日期2013-3-29