PHOSPHOINOSITIDE 3-KINASE - THE KEY SWITCH MECHANISM IN INSULIN SIGNALING

Insulin plays a key role in regulating a wide range of cellular proces ses. However, until recently little was known about the signalling pat hways that are involved in linking the insulin receptor with downstrea m responses. It is now apparent that the activation of class la phosph oinositide 3-kinase (PI 3-kinase) is necessary and in some cases suffi cient to elicit many of insulin's effects on glucose and lipid metabol ism. The lipid products of PI 3-kinase act as both membrane anchors an d allosteric regulators, serving to localize and activate downstream e nzymes and their protein substrates. One of the major ways these lipid products of PI 3-kinase act in insulin signalling is by binding to pl eckstrin homology (PH) domains of phosphoinositide-dependent protein k inase (PDK) and protein kinase B (PKB) and in the process regulating t he phosphorylation of PKB by PDR. Using mechanisms such as this, PI 3- kinase is able to act as a molecular switch to regulate the activity o f serine/threonine-specific kinase cascades important in mediating ins ulin's effects on endpoint responses.