PCTAIRE protein kinases interact directly with the COPII complex and modulate secretory cargo transport.
The export of secretory cargo from the endoplasmic reticulum is mediated by the COPII complex. In common with other aspects of intracellular transport, this step is regulated by protein kinase signalling. Recruitment of the COPII complex to the membrane is known to require ATP and to be blocked by the protein kinase inhibitor H-89. The identity of the specific protein kinase or kinases involved remains equivocal. Here we show that the Sec23p subunit of COPII interacts with PCTAIRE protein kinases. This interaction is shown using two-hybrid screening, direct binding and immunoprecipitation. Inhibition of PCTAIRE kinase activity by expression of a kinase-dead mutant, or specific depletion of PCTAIRE using RNAi, leads to defects in early secretory pathway function including cargo transport, as well as vesicular-tubular transport carrier (VTC) and Golgi localization. These data show a role for PCTAIRE protein kinase function in membrane traffic through the early secretory pathway.
Palmer
Krysten J
KJ
Department of Biochemistry, University of Bristol, School of Medical Science, University Walk, Bristol, BS8 1TD, UK.
Konkel
Joanne E
JE
Stephens
David J
DJ
D000818:Animals; D001692:Biological Transport / Q000502:physiology*; D022181:COP-Coated Vesicles / Q000378:metabolism*; D002460:Cell Line; D048430:Cell Shape; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D022142:Secretory Vesicles / Q000737:chemistry / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
D011993:Recombinant Fusion Proteins; C512739:SEC23A protein, human; D033921:Vesicular Transport Proteins; D017346:Protein Serine-Threonine Kinases; D018844:Cyclin-Dependent Kinases; C089463:PCTAIRE-1 protein kinase