Phosphoinositide 3-kinase: the key switch mechanism in insulin signalling

Phosphoinositide 3-kinase: the key switch mechanism in insulin signalling

1998 | Peter R. SHEPHERD*, Dominic J. WITHERS† and Kenneth SIDDLE‡
Insulin plays a crucial role in regulating various cellular processes, and the activation of class 1a phosphoinositide 3-kinase (PI 3-kinase) is essential for many of its effects on glucose and lipid metabolism. PI 3-kinase produces lipid products, such as phosphatidylinositol 3,4,5-trisphosphate (PIP3), which act as both membrane anchors and allosteric regulators, facilitating the localization and activation of downstream enzymes and their protein substrates. One major way PI 3-kinase acts in insulin signaling is by binding to pleckstrin homology (PH) domains of phosphoinositide-dependent protein kinase (PDK) and protein kinase B (PKB), regulating PKB phosphorylation by PDK. This review discusses the role of PI 3-kinase in insulin signaling, including the recruitment of PI 3-kinase to signaling complexes, the function of adapter/regulatory subunits, and the mechanisms by which PI 3-kinase activation leads to the activation of downstream signaling pathways. The review also highlights the importance of PIP3 as a signaling molecule and the potential roles of other proteins and domains in PI 3-kinase signaling.Insulin plays a crucial role in regulating various cellular processes, and the activation of class 1a phosphoinositide 3-kinase (PI 3-kinase) is essential for many of its effects on glucose and lipid metabolism. PI 3-kinase produces lipid products, such as phosphatidylinositol 3,4,5-trisphosphate (PIP3), which act as both membrane anchors and allosteric regulators, facilitating the localization and activation of downstream enzymes and their protein substrates. One major way PI 3-kinase acts in insulin signaling is by binding to pleckstrin homology (PH) domains of phosphoinositide-dependent protein kinase (PDK) and protein kinase B (PKB), regulating PKB phosphorylation by PDK. This review discusses the role of PI 3-kinase in insulin signaling, including the recruitment of PI 3-kinase to signaling complexes, the function of adapter/regulatory subunits, and the mechanisms by which PI 3-kinase activation leads to the activation of downstream signaling pathways. The review also highlights the importance of PIP3 as a signaling molecule and the potential roles of other proteins and domains in PI 3-kinase signaling.
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[slides and audio] Phosphoinositide 3-kinase%3A the key switch mechanism in insulin signalling.