title: The plexin-B1/Rac interaction inhibits PAK activation and enhances Sema4D ligand binding.
abstract: The small GTPase Rac has been implicated in growth cone guidance mediated by semaphorins and their receptors. Here we demonstrate that plexin-B1, a receptor for Semaphorin4D (Sema4D), and p21-activated kinase (PAK) can compete for the interaction with active Rac and plexin-B1 can inhibit Rac-induced PAK activation. We have also demonstrated that expression of active Rac enhances the ability of plexin-B1 to interact with Sema4D. Active Rac stimulates the localization of plexin-B1 to the cell surface. The enhancement in Sema4D binding depends on the ability of Rac to bind plexin-B1. These observations support a model where signaling between Rac and plexin-B1 is bidirectional; Rac modulates plexin-B1 activity and plexin-B1 modulates Rac function.
authors.affiliation: Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Haris G
authors.initials: HG
authors.lastname: Vikis
authors.forename: Weiquan
authors.initials: W
authors.lastname: Li
authors.forename: Kun-Liang
authors.initials: KL
authors.lastname: Guan
mesh_terms: D000818:Animals; D015703:Antigens, CD; D019921:Biotinylation; D019556:COS Cells; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019286:Endopeptidase K / Q000494:pharmacology; D004789:Enzyme Activation; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000737:chemistry*; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D040121:Semaphorin-3A; D039961:Semaphorins; D015398:Signal Transduction; D054462:p21-Activated Kinases; D020744:rac GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C093224:CD100 antigen; D006023:Glycoproteins; D008024:Ligands; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C492119:PLXNB1 protein, human; D011506:Proteins; D011956:Receptors, Cell Surface; D040121:Semaphorin-3A; D039961:Semaphorins; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D019286:Endopeptidase K; D020744:rac GTP-Binding Proteins