Journal of Biological Chemistry
Volume 278, Issue 7, 14 February 2003, Pages 5419-5426
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MECHANISMS OF SIGNAL TRANSDUCTION
Protein Kinase C Isoform-specific Differences in the Spatial-Temporal Regulation and Decoding of Metabotropic Glutamate Receptor1a-stimulated Second Messenger Responses*

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Metabotropic glutamate receptors (mGluRs) coupled via Gq to the hydrolysis of phosphoinositides stimulate Ca2+ and PKCβII 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 Ca2+, conventional PKCs exhibit isoform-specific oscillation patterns. PKCα and PKCβI 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 PKCβII translocation responses are observed in mGluR1a-expressing cells. PKCβI expression also promotes persistent increases in intracellular diacyglycerol concentrations in response to mGluR1a stimulation without affecting PKCβII oscillation patterns in the same cell. PKCβII 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 PKCβII cooperatively suppress PKCβI-like response patterns for PKCβII. 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.

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*

This work was supported by Canadian Institutes of Health Research Grant MA-15506 (to S. S. G. F.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§

These authors contributed equally to this work.

Recipient of a Canadian Hypertension Society/CIHR fellowship.

**

Recipient of Heart and Stroke Foundation of Canada MacDonald Scholarship, Premier's Research Excellence Award, and Canada Research Chair in Molecular Neuroscience.