PI3K Class IB Pathway in Neutrophils

Abstract

Activation of G i -coupled receptors in neutrophils stimulates class IB phosphoinositide 3-kinase (PI3K) (also known as PI3Kγ) through the combined actions of Gβγ subunits and the small guanosine triphosphatase (GTPase) Ras, resulting in the production of phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P 3 ] and phosphatidylinositol 3,4-bisphosphate [PI(3,4)P 2 ] in the plasma membrane. In most cases, the effectors of this pathway possess a pleckstrin homology (PH) domain that mediates the interaction with and regulation by these two lipid messengers. These direct effectors sit within a complex regulatory network that includes several other signaling pathways and that is responsible for the control of important neutrophil functions, including adhesion, chemotaxis, secretion, and the "respiratory burst" [activation of the nicotinamide adenosine diphosphate (NADPH) oxidase]. Although the molecular details that link the direct effectors of class IB PI3K to these complex cell responses are still largely unknown, these responses involve complex regulation of small GTPases of the Rac, Rho, and Arf families.