Arf GTP-binding proteins and membrane traffic

National Heart, Lung, And Blood Institute

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Abstract

We continue to evaluate the roles played by Arf6 and also Golgi-associated Arfs like Arf1 at the plasma membrane. GTP-binding proteins like Arf cycle between GTP-bound, active and GDP-bound, inactive forms. We have found that Arf1, typically thought to function at the Golgi complex, is required for ventral actin structures formed in response to phorbol ester treatment. Phorbol esters like PMA are tumor promoters and lead to the activation of protein kinase C and Src family kinases. These ventral actin structures represent a major re-organization of the cortical actin cytoskeleton and focal adhesions. This adds to the growing list of cellular activities occurring at the plasma membrane that now are thought to involve Arf1. All Arf protein share common effectors (stimulation of phospholipase D, and phosphatidylinositol 4-phosphate 5-kinase) however they may be activated by different guanine nucleotide exchange factors (GEFs) and GTP-ase activating proteins (GAPs). Furthermore these GEFs and GAPs themselves may have unique signaling and scaffolding functions giving rise to distinct signaling outputs.