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Science 318 (5847): 64-66

Copyright © 2007 by the American Association for the Advancement of Science

PI3K{gamma} Is a Key Regulator of Inflammatory Responses and Cardiovascular Homeostasis

Phillip T. Hawkins, and Len R. Stephens

Abstract: Class I phosphoinositide 3-kinase (PI3K) signaling pathways regulate several important cellular functions, including cellular growth, division, survival, and movement. Class IB PI3K (also known as PI3K{gamma}) links heterotrimeric GTP-binding protein–coupled receptors to these pathways. Activation of class IB PI3K results in the rapid synthesis of phosphatidylinositol-3,4,5-trisphosphate [PtdIns(3,4,5)P3] and its dephosphorylation product PtdIns(3,4)P2 in the plasma membrane. These two lipid messengers bind to pleckstrin homology domain–containing effectors that regulate a complex signaling web downstream of receptor activation. Characteristic features of this pathway are the regulation of protein kinases and the regulation of small guanosine triphosphatases that control cellular movement, adhesion, contraction, and secretion. Most of the ligands that activate class IB PI3K are involved in coordinating the body's response to injury and infection, and recent studies suggest that small molecule inhibitors of this enzyme may represent a novel class of anti-inflammatory therapeutic agents.

The Babraham Institute, Cambridge CB22 3AT, UK. E-mail: phillip.hawkins{at} (P.T.H.); len.stephens{at} (L.R.S.)

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