title: Differential requirement for RhoA GTPase depending on the cellular localization of protein kinase D.
abstract: This study explores the links between the GTPase RhoA and the serine kinase protein kinase D (PKD) during thymocyte development. The rationale is that RhoA and PKD regulate common biological responses during T cell development, but there is nothing known about their interdependence. In fibroblasts, Rho function is required for activation of PKD catalytic activity. However, the data show that activation of Rho is neither sufficient nor essential for PKD activation in T cells. One alternative explanation for the apparent convergence of PKD and Rho signaling in T cells is that PKD responses might be Rho-dependent. To address this latter possibility, we probed the Rho requirements for the actions of constitutively active PKD mutants in pre-T cells of transgenic mice. Active PKD can localize to either the plasma membrane or the cytosol, and we therefore compared the Rho requirements for the actions of membrane- or cytosol-localized PKD. Here we show that membrane-localized PKD regulation of pre-T cell differentiation is Rho-dependent, but the actions of cytosol-localized PKD are not. These studies demonstrate that a Rho requirement for PKD activation is not ubiquitous. Moreover, links between PKD and Rho are determined by the cellular location of PKD.
authors.affiliation: Division of Cell Biology and Immunology, Wellcome Trust Biocentre, University of Dundee, Dundee UK DD1 5EH, Scotland, United Kingdom.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mullin
authors.forename: Kurt
authors.initials: K
authors.lastname: Lightfoot
authors.forename: Ulrica
authors.initials: U
authors.lastname: Marklund
authors.forename: Doreen A
authors.initials: DA
authors.lastname: Cantrell
mesh_terms: D036002:ADP Ribose Transferases / Q000378:metabolism; D000818:Animals; D001905:Botulinum Toxins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003014:Clostridium botulinum / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008822:Mice, Transgenic; D011493:Protein Kinase C / Q000737:chemistry* / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000737:chemistry* / Q000502:physiology*
chemical_list: D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; C089212:protein kinase D; D011493:Protein Kinase C; D001905:Botulinum Toxins; D020742:rhoA GTP-Binding Protein