摘要：

tivation of PI 3-kinase could then serve to eliminate a Vav inhibitor and simultaneous- ly produce activators of Vav GEF activity. Vav is a member of a large family of mole- cules containing a Dbl homology domain and a PH domain that could be similarly regulated ( 1 ) . Ras activation of Rac is medi- ated by PI 3-kinase (19). RasV1ZC4"a Ras effector mutant that retains the ability to bind to and activate PI 3-kinase but not other Ras effectors (19, 20, 21), cooperated with wild-type Vav to induce membrane ruf- fling in REF-52 fibroblasts (Fig. 3), support- ing our suggestion that Ras activation of Rac is mediatqd by a Dbl-related molecule. Fur- thermore, regulation through the Dbl ho- mology and PH domains of Sos, a bifi~nc- tional GEF for both Ras and Rac, is appar- ently similar to the regulation that we have proposed for Vav (22). The regulation of Vav by both PI 3-kinase and a protein kinase is similar to the dual regulation of the PH domain containing protein kinase B (PKB/ AKT) (23). Perhaps such dual regulation is a general feature of signaling molecules with PH domains.

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