HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Murthy, K. S. Articles by Makhlouf, G. M. Search for Related Content PubMed PubMed Citation Articles by Murthy, K. S. Articles by Makhlouf, G. M. Social Bookmarking                      What's this?

J Biol Chem, Vol. 273, Issue 51, 34519-34526, December 18, 1998

Differential Regulation of Phospholipase A₂ (PLA₂)-dependent Ca²⁺ Signaling in Smooth Muscle by cAMP- and cGMP-dependent Protein Kinases
INHIBITORY PHOSPHORYLATION OF PLA₂ BY CYCLIC NUCLEOTIDE-DEPENDENT PROTEIN KINASES

From the Departments of Physiology and Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298-0711

Both cAMP- and cGMP-dependent protein kinases inhibit agonist-stimulated phospholipase C- (PLC-) activity and inositol 1,4,5-trisphosphate-dependent Ca²⁺ release in vascular and visceral smooth muscle. In smooth muscle of the intestinal longitudinal layer, however, the initial steps in Ca²⁺ mobilization involve activation of cytosolic PLA₂ (cPLA₂) and arachidonic acid (AA)-dependent stimulation of Ca²⁺ influx. The present study examined whether cAMP- and cGMP-dependent protein kinases are capable of regulating these processes also. Agents that activated cAMP-dependent protein kinase (5,6-dichloro-1--D-ribofuranosylbenzimidazole 3',5'-cyclic monophosphothioate (Sp-isomer) and isoproterenol), cGMP-dependent protein kinase (8-(4-chlorophenylthio)-guanosine 3',5'-cyclic monophosphate and Na nitroprusside), or both kinases (vasoactive intestinal peptide and isoproterenol >1 µM) induced phosphorylation of cPLA₂ and inhibition of agonist-stimulated cPLA₂ activity. Phosphorylation and inhibition of cPLA₂ activity by cAMP- and cGMP-dependent protein kinases were blocked by the corresponding selective inhibitors (cAMP-dependent protein kinase, N-[2(p-bromocinnamylamino)ethyl]-5-isoquinoline-sulfonamide hydrochloride (H-89) and myristoylated protein kinase inhibitor () amide; cGMP-dependent protein kinase, (8R,9S,11S)-()-9-methoxy-carbamyl-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H,11H,-2,7b,11a-trizadizobenzo(a,g)cycloocta(c,d,e)-trinden-1-one (KT-5823)). In contrast, AA-stimulated Ca²⁺ influx was inhibited by agents that activated cGMP-dependent protein kinase only; the inhibition was selectively blocked by KT-5823. The study provides the first evidence of inhibitory phosphorylation of cPLA₂ in vivo by cAMP- and cGMP-dependent protein kinases. Inhibition of cPLA₂ activity and AA-induced Ca²⁺ influx partly account for the ability of cAMP-dependent protein kinase and/or cGMP-dependent protein kinase to cause relaxation. Their importance resides in their location at the inception of the Ca²⁺ signaling cascade.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				J. Huang, S. Mahavadi, W. Sriwai, J. R. Grider, and K. S. Murthy Cross-regulation of VPAC2 receptor desensitization by M3 receptors via PKC-mediated phosphorylation of RKIP and inhibition of GRK2 Am J Physiol Gastrointest Liver Physiol, March 1, 2007; 292(3): G867 - G874. [Abstract] [Full Text] [PDF]

				J. Huang, H. Zhou, S. Mahavadi, W. Sriwai, and K. S. Murthy Inhibition of G{alpha}q-dependent PLC-beta1 activity by PKG and PKA is mediated by phosphorylation of RGS4 and GRK2 Am J Physiol Cell Physiol, January 1, 2007; 292(1): C200 - C208. [Abstract] [Full Text] [PDF]

				N. Flamand, J. Lefebvre, G. Lapointe, S. Picard, L. Lemieux, S. G. Bourgoin, and P. Borgeat Inhibition of platelet-activating factor biosynthesis by adenosine and histamine in human neutrophils: involvement of cPLA2{alpha} and reversal by lyso-PAF J. Leukoc. Biol., May 1, 2006; 79(5): 1043 - 1051. [Abstract] [Full Text] [PDF]

				S. Offer, S. Yedgar, O. Schwob, M. Krimsky, H. Bibi, A. Eliraz, Z. Madar, and D. Shoseyov Negative feedback between secretory and cytosolic phospholipase A2 and their opposing roles in ovalbumin-induced bronchoconstriction in rats Am J Physiol Lung Cell Mol Physiol, March 1, 2005; 288(3): L523 - L529. [Abstract] [Full Text] [PDF]

				M. Luo, S. M. Jones, S. M. Phare, M. J. Coffey, M. Peters-Golden, and T. G. Brock Protein Kinase A Inhibits Leukotriene Synthesis by Phosphorylation of 5-Lipoxygenase on Serine 523 J. Biol. Chem., October 1, 2004; 279(40): 41512 - 41520. [Abstract] [Full Text] [PDF]

				S. H. H. Chan, K.-F. Chang, C.-C. Ou, and J. Y. H. Chan Nitric Oxide Regulates c-fos Expression in Nucleus Tractus Solitarii Induced by Baroreceptor Activation via cGMP-Dependent Protein Kinase and cAMP Response Element-Binding Protein Phosphorylation Mol. Pharmacol., February 1, 2004; 65(2): 319 - 325. [Abstract] [Full Text] [PDF]

				C. Pavoine, N. Behforouz, C. Gauthier, S. Le Gouvello, F. Roudot-Thoraval, C. R. Martin, A. Pawlak, C. Feral, N. Defer, R. Houel, et al. {beta}2-Adrenergic Signaling in Human Heart: Shift from the Cyclic AMP to the Arachidonic Acid Pathway Mol. Pharmacol., November 1, 2003; 64(5): 1117 - 1125. [Abstract] [Full Text] [PDF]

				K. S. Murthy, H. Zhou, J. R. Grider, and G. M. Makhlouf Inhibition of sustained smooth muscle contraction by PKA and PKG preferentially mediated by phosphorylation of RhoA Am J Physiol Gastrointest Liver Physiol, June 1, 2003; 284(6): G1006 - G1016. [Abstract] [Full Text] [PDF]

				H. Zhou, S. Das, and K. S. Murthy Erk1/2- and p38 MAP kinase-dependent phosphorylation and activation of cPLA2 by m3 and m2 receptors Am J Physiol Gastrointest Liver Physiol, March 1, 2003; 284(3): G472 - G480. [Abstract] [Full Text] [PDF]

				K. S. Murthy and H. Zhou Selective phosphorylation of the IP3R-I in vivo by cGMP-dependent protein kinase in smooth muscle Am J Physiol Gastrointest Liver Physiol, February 1, 2003; 284(2): G221 - G230. [Abstract] [Full Text] [PDF]

				R. Feil, N. Gappa, M. Rutz, J. Schlossmann, C. R. Rose, A. Konnerth, S. Brummer, S. Kuhbandner, and F. Hofmann Functional Reconstitution of Vascular Smooth Muscle Cells With cGMP-Dependent Protein Kinase I Isoforms Circ. Res., May 31, 2002; 90(10): 1080 - 1086. [Abstract] [Full Text] [PDF]

				K. S. Murthy cAMP inhibits IP3-dependent Ca2+ release by preferential activation of cGMP-primed PKG Am J Physiol Gastrointest Liver Physiol, November 1, 2001; 281(5): G1238 - G1245. [Abstract] [Full Text] [PDF]

				S. Magne, D. Couchie, F. Pecker, and C. Pavoine beta 2-Adrenergic Receptor Agonists Increase Intracellular Free Ca2+ Concentration Cycling in Ventricular Cardiomyocytes through p38 and p42/44 MAPK-mediated Cytosolic Phospholipase A2 Activation J. Biol. Chem., October 19, 2001; 276(43): 39539 - 39548. [Abstract] [Full Text] [PDF]

				K. S. Murthy, J. R. Grider, and G. M. Makhlouf Heterologous desensitization of response mediated by selective PKC-dependent phosphorylation of Gi-1 and Gi-2 Am J Physiol Cell Physiol, October 1, 2000; 279(4): C925 - C934. [Abstract] [Full Text] [PDF]

				K. A. Lucas, G. M. Pitari, S. Kazerounian, I. Ruiz-Stewart, J. Park, S. Schulz, K. P. Chepenik, and S. A. Waldman Guanylyl Cyclases and Signaling by Cyclic GMP Pharmacol. Rev., September 1, 2000; 52(3): 375 - 414. [Abstract] [Full Text] [PDF]

				S. D. Koh, T. W. Kim, J. Y. Jun, N. J Glasgow, S. M Ward, and K. M Sanders Regulation of pacemaker currents in interstitial cells of Cajal from murine small intestine by cyclic nucleotides J. Physiol., August 15, 2000; 527(1): 149 - 162. [Abstract] [Full Text] [PDF]

				H.-P. Chu and A. M. Etgen Ovarian Hormone Dependence of alpha 1-Adrenoceptor Activation of the Nitric Oxide-cGMP Pathway: Relevance for Hormonal Facilitation of Lordosis Behavior J. Neurosci., August 15, 1999; 19(16): 7191 - 7197. [Abstract] [Full Text] [PDF]

				A. Ammendola, A. Geiselhoringer, F. Hofmann, and J. Schlossmann Molecular Determinants of the Interaction between the Inositol 1,4,5-Trisphosphate Receptor-associated cGMP Kinase Substrate (IRAG) and cGMP Kinase Ibeta J. Biol. Chem., June 22, 2001; 276(26): 24153 - 24159. [Abstract] [Full Text] [PDF]