title: Phospholipase Cgamma binds alpha1beta1 integrin and modulates alpha1beta1 integrin-specific adhesion.
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.
authors.affiliation: Institut für Molekularbiologie und Biochemie, Freie Universität Berlin, Arnimallee 22, D-14195 Berlin-Dahlem, Germany.
authors.forename: Dörte
authors.initials: D
authors.lastname: Vossmeyer
authors.forename: Werner
authors.initials: W
authors.lastname: Hofmann
authors.forename: Klemens
authors.initials: K
authors.lastname: Löster
authors.forename: Werner
authors.initials: W
authors.lastname: Reutter
authors.forename: Kerstin
authors.initials: K
authors.lastname: Danker
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D002448:Cell Adhesion; D003094:Collagen / Q000737:chemistry; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D007074:Immunoglobulin G / Q000378:metabolism; D039222:Integrin alpha1beta1; D016023:Integrins / Q000737:chemistry* / Q000378:metabolism*; D007527:Isoenzymes / Q000737:chemistry* / Q000378:metabolism*; D007797:Laminin / Q000737:chemistry; D008954:Models, Biological; D008969:Molecular Sequence Data; D016716:PC12 Cells; D010455:Peptides / Q000737:chemistry; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051966:Phospholipase C gamma; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D013997:Time Factors; D014162:Transfection; D010738:Type C Phospholipases / Q000737:chemistry* / Q000378:metabolism*; D014443:Tyrosine / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D004963:Estrenes; D007074:Immunoglobulin G; D039222:Integrin alpha1beta1; D016023:Integrins; D007527:Isoenzymes; D007797:Laminin; D010455:Peptides; D010726:Phosphodiesterase Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D014443:Tyrosine; D003094:Collagen; D010738:Type C Phospholipases; D051966:Phospholipase C gamma