Gbetagamma-mediated regulation of Golgi organization is through the direct activation of protein kinase D.
We have shown previously that the betagamma subunits of the heterotrimeric G proteins regulate the organization of the pericentriolarly localized Golgi stacks. In this report, evidence is presented that the downstream target of Gbetagamma is protein kinase D (PKD), an isoform of protein kinase C. PKD, unlike other members of this class of serine/threonine kinases, contains a pleckstrin homology (PH) domain. Our results demonstrate that Gbetagamma directly activates PKD by interacting with its PH domain. Inhibition of PKD activity through the use of pharmacological agents, synthetic peptide substrates, and, more specifically, the PH domain of PKD prevents Gbetagamma-mediated Golgi breakdown. Our findings suggest a possible mechanism by which the direct interaction of Gbetagamma with PKD regulates the dynamics of Golgi membranes and protein secretion.
Jamora
C
C
Biology Department, University of California, San Diego, La Jolla 92093, USA.
Yamanouye
N
N
Van Lint
J
J
Laudenslager
J
J
Vandenheede
J R
JR
Faulkner
D J
DJ
Malhotra
V
V
D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D002460:Cell Line; D018076:DNA, Complementary; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006056:Golgi Apparatus / Q000502:physiology* / Q000648:ultrastructure; D020962:Heterotrimeric GTP-Binding Proteins; D006801:Humans; D007700:Kinetics; D008562:Membrane Glycoproteins; D051379:Mice; D011493:Protein Kinase C / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D014721:Vesicular stomatitis Indiana virus; D014759:Viral Envelope Proteins / Q000493:pharmacokinetics; D018909:src Homology Domains
D018076:DNA, Complementary; D004791:Enzyme Inhibitors; C028391:G protein, vesicular stomatitis virus; C118981:G-protein Beta gamma; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; C089212:protein kinase D; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D020962:Heterotrimeric GTP-Binding Proteins