title: The actin-binding protein profilin binds to PIP2 and inhibits its hydrolysis by phospholipase C.
abstract: Profilin is generally thought to regulate actin polymerization, but the observation that acidic phospholipids dissociate the complex of profilin and actin raised the possibility that profilin might also regulate lipid metabolism. Profilin isolated from platelets binds with high affinity to small clusters of phosphatidylinositol 4,5-bisphosphate (PIP2) molecules in micelles and also in bilayers with other phospholipids. The molar ratio of the complex of profilin with PIP2 is 1:7 in micelles of pure PIP2 and 1:5 in bilayers composed largely of other phospholipids. Profilin competes efficiently with platelet cytosolic phosphoinositide-specific phospholipase C for interaction with the PIP2 substrate and thereby inhibits PIP2 hydrolysis by this enzyme. The cellular concentrations and binding characteristics of these molecules are consistent with profilin being a negative regulator of the phosphoinositide signaling pathway in addition to its established function as an inhibitor of actin polymerization.
authors.affiliation: Department of Cell Biology and Anatomy, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors.forename: P J
authors.initials: PJ
authors.lastname: Goldschmidt-Clermont
authors.forename: L M
authors.initials: LM
authors.lastname: Machesky
authors.forename: J J
authors.initials: JJ
authors.lastname: Baldassare
authors.forename: T D
authors.initials: TD
authors.lastname: Pollard
mesh_terms: D000199:Actins / Q000378:metabolism*; D002850:Chromatography, Gel; D003285:Contractile Proteins; D006801:Humans; D006868:Hydrolysis; D008823:Micelles; D008840:Microfilament Proteins / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism*; D011108:Polymers; D051304:Profilins; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000199:Actins; D003285:Contractile Proteins; D008823:Micelles; D008840:Microfilament Proteins; C495738:PFN1 protein, human; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D011108:Polymers; D051304:Profilins; D010738:Type C Phospholipases