Receptor-activated phosphoinositide (PI) 3-kinases produce PtdIns(3,4,5)P 3 and its metabolite PtdIns(3,4)P 2 that function as second messengers in membrane recruitment and activation of target proteins. The cytohesin and centaurin protein families are potential targets for PtdIns(3,4,5)P 3 that also regulate and interact with Arf GTPases. Consequently, these families are poised to transduce PI 3-kinase activation into coordinated control of Arf-dependent pathways. Proposed downstream events in PI 3-kinase-regulated Arf cascades include modulation of vesicular trafficking and the actin cytoskeleton. Copyright (C) 2000 Elsevier Science Ltd.