Leukocyte Activation by Chemoattractant Receptors: Roles of a Guanine Nucleotide Regulatory Protein and Polyphosphoinositide Metabolism

Chemoattractant receptors on leukocytes are coupled to a guanine nucleotide regulatory (N or G) protein that stimulates a membrane-associated phospholipase C to hydrolyze phosphatidylinositol 4,5-biphosphate. The products of this hydrolysis are inositol 1,4,5-trisphosphate and 1,2-diacylglycerol, which act as second messengers by raising intracellular levels of Ca++ and activating protein kinase C, respectively. These processes promote cellular activation but also initiate reactions that feed back to inhibit the stimulatory pathway.