title: PKD: a new protein kinase C-dependent pathway in platelets.
abstract: Protein kinase D (PKD, also known as PKCmu) is closely related to the protein kinase C superfamily but is differentially regulated and has a distinct catalytic domain that shares homology with Ca(2+)-dependent protein kinases. PKD is highly expressed in hematopoietic cells and undergoes rapid and sustained activation upon stimulation of immune receptors. PKD is regulated through phosphorylation by protein kinase C (PKC). In the present study, we show that PKD is expressed in human platelets and that it is rapidly activated by receptors coupled to heterotrimeric G-proteins or tyrosine kinases. Activation of PKD is mediated downstream of PKC. Strong agonists such as convulxin, which acts on GPVI, and thrombin cause sustained activation of PKC and PKD, whereas the thromboxane mimetic U46619 gives rise to transient activation of PKC and PKD. Activation of PKD by submaximal concentrations of phospholipase C-coupled receptor agonists is potentiated by G(i)-coupled receptors (eg, adenosine diphosphate and epinephrine). This study shows that PKD is rapidly activated by a wide variety of platelet agonists through a PKC-dependent pathway. Activation of PKD enables phosphorylation of a distinct set of substrates to those targeted by PKC in platelets.
authors.affiliation: Department of Biochemistry, University of Oxford, United Kingdom. margaret@bioch.ox.ac.uk
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Stafford
authors.forename: Steve P
authors.initials: SP
authors.lastname: Watson
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Pears
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D001792:Blood Platelets / Q000201:enzymology*; D015153:Blotting, Western; D003435:Crotalid Venoms / Q000494:pharmacology; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology; D020962:Heterotrimeric GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D007163:Immunosorbent Techniques; D037181:Lectins, C-Type; D010766:Phosphorylation; D010980:Platelet Membrane Glycoproteins / Q000494:pharmacology; D011493:Protein Kinase C / Q000097:blood*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
chemical_list: D003435:Crotalid Venoms; D037181:Lectins, C-Type; D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI; C028890:convulxin; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C089212:protein kinase D; D011493:Protein Kinase C; D013917:Thrombin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D020962:Heterotrimeric GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate; D004837:Epinephrine