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Regulation by cAMP-dependent protein kinease of a G-protein-mediated phospholipase C

Liu, Mingyao and Simon, Melvin I. (1996) Regulation by cAMP-dependent protein kinease of a G-protein-mediated phospholipase C. Nature, 382 (6586). pp. 83-87. ISSN 0028-0836. doi:10.1038/382083a0.

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The heterotrimeric G proteins mediate a variety of cellular processes by coupling transmembrane receptors to different effector molecules, including adenylyl cyclases and inositol-phospholipid-specific phospholipase C (PLC). Activation of adenylyl cyclases results in the production of cyclic AMP and activation of cAMP-dependent protein kinase (PKA). Phospholipase C catalyses the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PtdInsP_2) to generate diacylglycerol and inositol-1,4,5-triphosphate (InsP^3), leading to the activation of protein kinase C (PKC) and the mobilization of intracellular calcium. The various PLC isoforms appear to be activated by different receptors, and in some cases by different G-protein components. There are four well-characterized forms of PLC-β and all of them are activated to various extents by the Gα_q family of G proteins. Specific activation of PLC isoforms β2 and β3 by; G-protein βγ subunits has also been reported. Although it has been suggested that PLC activity might be modulated by the adenylyl cyclase pathway, no clear link has been established between the two pathways. Here we report that cAMP-dependent protein kinase specifically inhibits Gβγ-activated PLC-β2 activity but not that of the Gα-activated PLC isoforms, and that the effect of PKA is not mimicked by PKC isozymes. Furthermore, we show that PKA directly phosphorylates serine residues of the PLC-β2 protein both in vivo and in vitro. Our results provide an insight into the specificity and nature of the crosstalk between the two G-protein-coupled signal transduction pathways.

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Additional Information:© 1996 Nature Publishing Group. Received 21 February; accepted 14 May 1996. We thank M. D. Uhler (University of Michigan) for cDNA clones of the catalytic subunit of the cAMP-dependent protein kinase, P. J. Parker (Imperial Cancer Research Fund, London) for cDNA clones of protein kinase C isotypes, and L. Alex, G. Sanna, L. Brundage, S. Offermanns, B. Yu, A. Aragay, J. Chen, S. Klumpp and D. Wu for their comments and discussions. This work was supported by a grant from the NIH.
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Issue or Number:6586
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Official Citation:Regulation by cAMP-dependent protein kinease of a G-protein-mediated phospholipase C 83-87 Mingyao Liu & Melvin I. Simon doi:10.1038/382083a0
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:58177
Deposited By: Ruth Sustaita
Deposited On:11 Jun 2015 16:06
Last Modified:10 Nov 2021 22:00

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