title: Intracellular location and cell context-dependent function of protein kinase D.
abstract: Protein kinase D (PKD) is an antigen receptor-activated serine kinase localized at either the plasma membrane or the cytosol of lymphocytes. To probe PKD function at these different locations, transgenesis was used to target active PKD either to the membrane or cytosol of pre-T cells. In recombinase gene null pre-T cells, membrane and cytosolic active PKD both induced differentiation reminiscent of beta selection: downregulation of CD25 and upregulation of CD2 and CD5. Active PKDs also induced pre-T cell proliferation, although this response was not universal to all thymocyte subsets. There were two striking differences between the actions of the differentially localized PKDs. Membrane but not cytosolic PKD could induce expression of CD8 and CD4 in recombinase null mice; cytosolic but not membrane PKD suppressed Vbeta to DJbeta rearrangements of the TCRbeta chain locus in wild-type T cells. PKD function is thus determined by its intracellular location and cell context.
authors.affiliation: Lymphocyte Activation Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom.
authors.forename: Ulrica
authors.initials: U
authors.lastname: Marklund
authors.forename: Kurt
authors.initials: K
authors.lastname: Lightfoot
authors.forename: Doreen
authors.initials: D
authors.lastname: Cantrell
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D051379:Mice; D009154:Mutation; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism
chemical_list: D011948:Receptors, Antigen, T-Cell; C089212:protein kinase D; D011493:Protein Kinase C