The plexin-B1/Rac interaction inhibits PAK activation and enhances Sema4D ligand binding.
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.
Vikis
Haris G
HG
Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Li
Weiquan
W
Guan
Kun-Liang
KL
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*
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