Protein kinase C isoform-specific differences in the spatial-temporal regulation and decoding of metabotropic glutamate receptor1a-stimulated second messenger responses.
Metabotropic glutamate receptors (mGluRs) coupled via Gq to the hydrolysis of phosphoinositides stimulate Ca(2+) and PKCbetaII oscillations in both excitable and non-excitable cells. In the present study, we show that mGluR1a activation stimulates the repetitive plasma membrane translocation of each of the conventional and novel, but not atypical, PKC isozymes. However, despite similarities in sequence and cofactor regulation by diacyglycerol and Ca(2+), conventional PKCs exhibit isoform-specific oscillation patterns. PKCalpha and PKCbetaI display three distinct patterns of activity: (1) agonist-independent oscillations, (2) agonist-stimulated oscillations, and (3) persistent plasma membrane localization in response to mGluR1a activation. In contrast, only agonist-stimulated PKCbetaII translocation responses are observed in mGluR1a-expressing cells. PKCbetaI expression also promotes persistent increases in intracellular diacyglycerol concentrations in response to mGluR1a stimulation without affecting PKCbetaII oscillation patterns in the same cell. PKCbetaII isoform-specific translocation patterns are regulated by specific amino acid residues localized within the C-terminal PKC V5 domain. Specifically, Asn-625 and Lys-668 localized within the V5 domain of PKCbetaII cooperatively suppress PKCbetaI-like response patterns for PKCbetaII. Thus, redundancy in PKC isoform expression and differential decoding of second messenger response provides a novel mechanism for generating cell type-specific responses to the same signal.
Babwah
Andy V
AV
Cell Biology Research Group, Robarts Research Institute, University of Western Ontario, 100 Perth Drive, London, Ontario N6A 5K8, Canada.
Dale
Lianne B
LB
Ferguson
Stephen S G
SS
D002460:Cell Line; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D009928:Organ Specificity; D011493:Protein Kinase C / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D015290:Second Messenger Systems; D015398:Signal Transduction
D007527:Isoenzymes; D018094:Receptors, Metabotropic Glutamate; D011493:Protein Kinase C