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Phospholipase Cgamma binds alpha1beta1 integrin and modulates alpha1beta1 integrin-specific adhesion.

Dörte Vossmeyer·Werner Hofmann·Klemens Löster·Werner Reutter·Kerstin Danker
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Abstract

Integrin adhesion receptors have been implicated in bidirectional signal transduction. The dynamic regulation of integrin affinity and avidity as well as post-ligand effects involved in outside-in signaling depends on the interaction of integrins with cytoskeletal and signaling proteins. In this study, we attempted to identify cytoplasmic binding partners of alpha(1)beta(1) integrin. We were able to show that cell adhesion to alpha(1)beta(1)-specific substrates results in the association of phospholipase Cgamma (PLCgamma) with the alpha(1)beta(1) integrin independent of PLCgamma tyrosine phosphorylation. Using peptide-binding assays, the membrane proximal sequences within the alpha(1)beta(1) integrin subunits were identified as binding sites for PLCgamma. In particular, the conserved sequence of beta(1) subunit binds the enzyme very efficiently. Because purified PLCgamma also binds the integrin peptides, binding seems to be direct. Inhibition of PLC by leads to reduced cell adhesion on alpha(1)beta(1)-specific substrates. Cells lacking the conserved domain of the alpha(1) subunit fail to respond to the PLC inhibition, indicating that this domain is necessary for PLC-dependent adhesion modulation of alpha(1)beta(1) integrin.

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Amino Acid MotifsAmino Acid SequenceAnimalsBlotting, WesternCHO CellsCell AdhesionCollagenCricetinaeCytoplasmDose-Response Relationship, DrugElectrophoresis, Polyacrylamide GelEnzyme InhibitorsEstrenesImmunoglobulin GIntegrin alpha1beta1IntegrinsIsoenzymesLamininModels, BiologicalMolecular Sequence DataPC12 CellsPeptidesPhosphodiesterase InhibitorsPhosphoinositide-3 Kinase InhibitorsPhospholipase C gammaPhosphorylationPrecipitin TestsProtein BindingProtein Structure, TertiaryPyrrolidinonesRatsTime FactorsTransfectionType C PhospholipasesTyrosineJournal ArticleResearch Support, Non-U.S. Gov't

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Dörte Vossmeyer, Werner Hofmann, Klemens Löster, Werner Reutter, Kerstin Danker. 2001-11-27. Phospholipase Cgamma binds alpha1beta1 integrin and modulates alpha1beta1 integrin-specific adhesion.. https://doi.org/10.1074/jbc.m105415200

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