A PIP5 Kinase Essential for Efficient Chemotactic Signaling

摘要: Summary In neutrophils and Dictyostelium , chemoattractant gradients generate directed cell migration by eliciting signaling events that bias intrinsic motility favor the production retention of upgradient pseudopods [1, 2]. Phosphoinositides are actively regulated during chemotaxis in these cells, most iconically PI(3,4,5)P 3 within plasma membrane [3, 4]. Although it is now known nonessential for gradient sensing [5, 6], role related phosphoinositide PI(4,5)P 2 little understood, despite its clear importance many biological processes [7]. We describe here a PIP5 kinase, PikI, which produces essential efficient cells. Without levels reduced 90%, while pikI − cells move at normal speeds, they highly disorientated cAMP gradients. Following chemotactic stimulation, Ras efficiently activated yet Ras-dependent responses (including activation PKB) severely impaired. PikI phosphorylated PKB [8], in vitro studies phosphomimic mutant suggest this phosphorylation increases activity. propose adequate required to couple downstream effectors making crucial player sensing.