Model for leukocyte regulation by chemoattractant receptors: roles of a guanine nucleotide regulatory protein and polyphosphoinositide metabolism.
Binding of chemoattractants to their receptors on phagocytes activates a guanine nucleotide regulatory (N) protein through the substitution of GTP for GDP on N. The activated N protein in turn stimulates a membrane-associated phospholipase C by lowering the Ca2+ concentration required to activate this enzyme from supraphysiologic levels to ambient intracellular concentrations. The phospholipase C hydrolyzes phosphatidylinositol 4,5-bisphosphate into the Ca2+ mobilizer inositol 1,4,5-trisphosphate and the protein kinase C activator 1,2-diacylglycerol. In addition to promoting cellular activation, the products of this hydrolysis initiate processes which feed back to inhibit poly-phosphoinositide breakdown. The regulatory model proposed herein may be relevant to other receptors which stimulate polyphosphoinositide metabolism.
D000262:Adenylyl Cyclases / Q000502:physiology; D002630:Chemotactic Factors / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D000242:Cyclic AMP / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology*; D008954:Models, Biological; D010587:Phagocytosis; D010716:Phosphatidylinositols / Q000502:physiology*; D011494:Protein Kinases / Q000502:physiology; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000502:physiology*
D002630:Chemotactic Factors; D010716:Phosphatidylinositols; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D000242:Cyclic AMP; D011494:Protein Kinases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases