Caspase 8 promotes peripheral localization and activation of Rab5.

ABSTRACT: Caspase 8 is a cysteine protease that initiates apoptotic signaling via the extrinsic pathway in a manner dependent upon association with early endosomes. Previously, we identified caspase 8 as an effector of migration, promoting motility in a manner dependent upon phosphorylation on Tyr-380 by Src family kinases and its subsequent association with Src homology 2 domain-containing proteins. Here we demonstrate the regulation of the small GTPase Rab5, which mediates early endosome formation, homotypic fusion, and maturation by caspase 8. Regulation requires the Tyr-380 phosphorylation site but not caspase proteolytic activity. Tyr-380 is essential for interaction with the Src homology 2 domains of p85alpha, a multifunctional adaptor for phosphatidylinositol 3-kinase, that possesses Rab-GAP

SUBMITTER: Torres VA 

PROVIDER: S-EPMC2605999 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature