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• W2107155498 endingPage "1079" @default.
• W2107155498 startingPage "1071" @default.
• W2107155498 abstract "Pleckstrin homology (PH) domains are sequences of ∼100 amino acids that form “modules” that have been proposed to facilitate protein/protein or protein/lipid interactions. Pleckstrin, first described as a substrate for protein kinase C in platelets and leukocytes, is composed of two PH domains, one at each end of the molecule, flanking an intervening sequence of 147 residues. Evidence is accumulating to support the hypothesis that PH domains are structural motifs that target molecules to membranes, perhaps through interactions with Gβγ or phosphatidylinositol 4,5-bisphosphate (PIP2), two putative PH domain ligands. In the present studies, we show that pleckstrin associates with membranes in human platelets. We further demonstrate that, in transfected Cos-1 cells, pleckstrin associates with peripheral membrane ruffles and dorsal membrane projections. This association depends on phosphorylation of pleckstrin and requires the presence of its NH2-terminal, but not its COOH-terminal, PH domain. Moreover, PH domains from other molecules cannot effectively substitute for pleckstrin's NH2terminal PH domain in directing membrane localization. Lastly, we show that wild-type pleckstrin actually promotes the formation of membrane projections from the dorsal surface of transfected cells, and that this morphologic change is similarly PH domain dependent. Since we have shown previously that pleckstrin-mediated inhibition of PIP2 metabolism by phospholipase C or phosphatidylinositol 3-kinase also requires pleckstrin phosphorylation and an intact NH2-terminal PH domain, these results suggest that: (a) pleckstrin's NH2terminal PH domain may regulate pleckstrin's activity by targeting it to specific areas within the cell membrane; and (b) pleckstrin may affect membrane structure, perhaps via interactions with PIP2 and/or other membrane-bound ligands." @default.
• W2107155498 created "2016-06-24" @default.
• W2107155498 creator A5026127942 @default.
• W2107155498 creator A5027992566 @default.
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• W2107155498 date "1997-03-10" @default.
• W2107155498 modified "2023-09-26" @default.
• W2107155498 title "Pleckstrin Associates with Plasma Membranes and Induces the Formation of Membrane Projections: Requirements for Phosphorylation and the NH2-terminal PH Domain" @default.
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• W2107155498 doi "https://doi.org/10.1083/jcb.136.5.1071" @default.
• W2107155498 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2132483" @default.
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• W2107155498 hasPublicationYear "1997" @default.
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