title: The IκB kinase complex is required for plexin-B-mediated activation of RhoA.
abstract: Plexins are widely expressed transmembrane proteins that mediate the cellular effects of semaphorins. The molecular mechanisms of plexin-mediated signal transduction are still poorly understood. Here we show that signalling via B-family plexins leading to the activation of the small GTPase RhoA requires activation of the IκB kinase (IKK)-complex. In contrast, plexin-B-dependent regulation of R-Ras activity is not affected by IKK activity. This regulation of plexin signalling depends on the kinase activity of the IKK-complex, but is independent of NF-κB activation. We confirm that the IKK-complex is active in tumour cells and osteoblasts, and we demonstrate that plexin-B-dependent tumour cell invasiveness and regulation of osteoblast differentiation require an active IKK-complex. This study identifies a novel, NF-κB-independent function of the IKK-complex and shows that IKK directs plexin-B signalling to the activation of RhoA.
authors.affiliation: Max-Planck-Institute for Heart and Lung Research, Department of Pharmacology, Bad Nauheim, Germany; Institute of Pharmacology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Zielonka
authors.affiliation: Max-Planck-Institute for Heart and Lung Research, Department of Pharmacology, Bad Nauheim, Germany.
authors.forename: Ramesh K
authors.initials: RK
authors.lastname: Krishnan
authors.affiliation: Max-Planck-Institute for Heart and Lung Research, Department of Pharmacology, Bad Nauheim, Germany.
authors.forename: Jakub M
authors.initials: JM
authors.lastname: Swiercz
authors.affiliation: Max-Planck-Institute for Heart and Lung Research, Department of Pharmacology, Bad Nauheim, Germany; Medical Faculty, University of Frankfurt, Frankfurt am Main, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Offermanns
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D061986:MCF-7 Cells; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; C091529:plexin; D051550:I-kappa B Kinase; D020742:rhoA GTP-Binding Protein