J. Biol. Chem., Vol. 262, Issue 27, 13111-13119, 09, 1987

Inhibition of intracellular cAMP-dependent protein kinase using mutant genes of the regulatory type I subunit

CH Clegg, LA Correll, GG Cadd and GS McKnight
Department of Pharmacology, University of Washington, Seattle 98195.

Expression vectors were constructed that code for mutated forms of the regulatory type 1 subunit (RI) of cyclic AMP-dependent protein kinase. These mutations alter a specific amino acid which is present in each of two homologous cAMP-binding domains of the RI protein. When these expression vectors were introduced into NIH 3T3 and Y1 adrenocortical tumor cells a mutant RI protein was produced that acted in a dominant fashion to cause a 20-400-fold inhibition of cAMP-dependent protein kinase activation. In addition, processes controlled by cAMP in adrenal cells were blocked; cells became resistant to the growth-inhibitory effects of cAMP and defective in steroid synthesis. Expression of mutant RI genes in cells provides a specific means to explore the role of cAMP and protein phosphorylation in the process of intracellular signalling.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. N. Gelinas, G. Tenorio, N. Lemon, T. Abel, and P. V. Nguyen {beta}-Adrenergic receptor activation during distinct patterns of stimulation critically modulates the PKA-dependence of LTP in the mouse hippocampus Learn. Mem., April 25, 2008; 15(5): 281 - 289. [Abstract] [Full Text] [PDF]

				T. L. McCarthy, R. B. Hochberg, D. C. Labaree, and M. Centrella 3-Ketosteroid Reductase Activity and Expression by Fetal Rat Osteoblasts J. Biol. Chem., November 23, 2007; 282(47): 34003 - 34012. [Abstract] [Full Text] [PDF]

				T. L. McCarthy, T. H. Pham, B. I. Knoll, and M. Centrella Prostaglandin E2 Increases Transforming Growth Factor-{beta} Type III Receptor Expression through CCAAT Enhancer-Binding Protein {delta} in Osteoblasts Mol. Endocrinol., November 1, 2007; 21(11): 2713 - 2724. [Abstract] [Full Text] [PDF]

				T. Yamamoto, H. Shimano, N. Inoue, Y. Nakagawa, T. Matsuzaka, A. Takahashi, N. Yahagi, H. Sone, H. Suzuki, H. Toyoshima, et al. Protein Kinase A Suppresses Sterol Regulatory Element-binding Protein-1C Expression via Phosphorylation of Liver X Receptor in the Liver J. Biol. Chem., April 20, 2007; 282(16): 11687 - 11695. [Abstract] [Full Text] [PDF]

				C. Isiegas, A. Park, E. R. Kandel, T. Abel, and K. M. Lattal Transgenic Inhibition of Neuronal Protein Kinase A Activity Facilitates Fear Extinction J. Neurosci., December 6, 2006; 26(49): 12700 - 12707. [Abstract] [Full Text] [PDF]

				K. A. Burton, D. A. McDermott, D. Wilkes, M. N. Poulsen, M. A. Nolan, M. Goldstein, C. T. Basson, and G. S. McKnight Haploinsufficiency at the Protein Kinase A RI{alpha} Gene Locus Leads to Fertility Defects in Male Mice and Men Mol. Endocrinol., October 1, 2006; 20(10): 2504 - 2513. [Abstract] [Full Text] [PDF]

				L. C. Muniz, G. Yehia, E. Memin, P. V.A.L. Ratnakar, and C. A. Molina Transcriptional Regulation of Cyclin D2 by the PKA Pathway and Inducible cAMP Early Repressor in Granulosa Cells Biol Reprod, August 1, 2006; 75(2): 279 - 288. [Abstract] [Full Text] [PDF]

				R. F. Watson, R. M. Abdel-Majid, M. W. Barnett, B. S. Willis, A. Katsnelson, T. H. Gillingwater, G. S. McKnight, P. C. Kind, and P. E. Neumann Involvement of protein kinase A in patterning of the mouse somatosensory cortex. J. Neurosci., May 17, 2006; 26(20): 5393 - 5401. [Abstract] [Full Text] [PDF]

				K. S. Nadella and L. S. Kirschner Disruption of Protein Kinase A Regulation Causes Immortalization and Dysregulation of D-Type Cyclins Cancer Res., November 15, 2005; 65(22): 10307 - 10315. [Abstract] [Full Text] [PDF]

				T. Yoshida and M. Mishina Distinct Roles of Calcineurin-Nuclear Factor of Activated T-Cells and Protein Kinase A-cAMP Response Element-Binding Protein Signaling in Presynaptic Differentiation J. Neurosci., March 23, 2005; 25(12): 3067 - 3079. [Abstract] [Full Text] [PDF]

				M. D. Johnson, L.-R. Yu, T. P. Conrads, Y. Kinoshita, T. Uo, J. D. Matthews, S.-W. Lee, R. D. Smith, T. D. Veenstra, and R. S. Morrison Proteome Analysis of DNA Damage-induced Neuronal Death Using High Throughput Mass Spectrometry J. Biol. Chem., June 18, 2004; 279(25): 26685 - 26697. [Abstract] [Full Text] [PDF]

				K. M. Zawadzki and S. S. Taylor cAMP-dependent Protein Kinase Regulatory Subunit Type II{beta}: ACTIVE SITE MUTATIONS DEFINE AN ISOFORM-SPECIFIC NETWORK FOR ALLOSTERIC SIGNALING BY cAMP J. Biol. Chem., February 20, 2004; 279(8): 7029 - 7036. [Abstract] [Full Text] [PDF]

				S. Klein-Hessling, M. K. Jha, B. Santner-Nanan, F. Berberich-Siebelt, T. Baumruker, A. Schimpl, and E. Serfling Protein Kinase A Regulates GATA-3-Dependent Activation of IL-5 Gene Expression in Th2 Cells J. Immunol., March 15, 2003; 170(6): 2956 - 2961. [Abstract] [Full Text] [PDF]

				P. S. Amieux, D. G. Howe, H. Knickerbocker, D. C. Lee, T. Su, G. S. Laszlo, R. L. Idzerda, and G. S. McKnight Increased Basal cAMP-dependent Protein Kinase Activity Inhibits the Formation of Mesoderm-derived Structures in the Developing Mouse Embryo J. Biol. Chem., July 19, 2002; 277(30): 27294 - 27304. [Abstract] [Full Text] [PDF]

				B. Yusta, J. Estall, and D. J. Drucker Glucagon-like Peptide-2 Receptor Activation Engages Bad and Glycogen Synthase Kinase-3 in a Protein Kinase A-dependent Manner and Prevents Apoptosis following Inhibition of Phosphatidylinositol 3-Kinase J. Biol. Chem., July 5, 2002; 277(28): 24896 - 24906. [Abstract] [Full Text] [PDF]

				J.-P. Pursiheimo, J. Saari, M. Jalkanen, and M. Salmivirta Cooperation of Protein Kinase A and Ras/ERK Signaling Pathways Is Required for AP-1-mediated Activation of Fibroblast Growth Factor-inducible Response Element (FiRE) J. Biol. Chem., July 5, 2002; 277(28): 25344 - 25355. [Abstract] [Full Text] [PDF]

				P. Repovic and E. N. Benveniste Prostaglandin E2 Is a Novel Inducer of Oncostatin-M Expression in Macrophages and Microglia J. Neurosci., July 1, 2002; 22(13): 5334 - 5343. [Abstract] [Full Text] [PDF]

				T. Yoshida, A. Ito, N. Matsuda, and M. Mishina Regulation by Protein Kinase A Switching of Axonal Pathfinding of Zebrafish Olfactory Sensory Neurons through the Olfactory Placode-Olfactory Bulb Boundary J. Neurosci., June 15, 2002; 22(12): 4964 - 4972. [Abstract] [Full Text] [PDF]

				P. S. AMIEUX and G. S. MCKNIGHT The Essential Role of RI{alpha} in the Maintenance of Regulated PKA Activity Ann. N.Y. Acad. Sci., June 1, 2002; 968(1): 75 - 95. [Abstract] [Full Text] [PDF]

				Y. Huang, H. Roelink, and G. S. McKnight Protein Kinase A Deficiency Causes Axially Localized Neural Tube Defects in Mice J. Biol. Chem., May 24, 2002; 277(22): 19889 - 19896. [Abstract] [Full Text] [PDF]

				O. Asher, T. D. Cunningham, L. Yao, A. S. Gordon, and I. Diamond Ethanol Stimulates cAMP-Responsive Element (CRE)-Mediated Transcription via CRE-Binding Protein and cAMP-Dependent Protein Kinase J. Pharmacol. Exp. Ther., April 1, 2002; 301(1): 66 - 70. [Abstract] [Full Text] [PDF]

				B. S. Skalhegg, Y. Huang, T. Su, R. L. Idzerda, G. S. McKnight, and K. A. Burton Mutation of the C{alpha} Subunit of PKA Leads to Growth Retardation and Sperm Dysfunction Mol. Endocrinol., March 1, 2002; 16(3): 630 - 639. [Abstract] [Full Text] [PDF]

				W. Chen, Y.-L. Yu, S.-F. Lee, Y.-J. Chiang, J.-R. Chao, J.-H. Huang, J.-H. Chiong, C.-J. Huang, M.-Z. Lai, H.-F. Yang-Yen, et al. CREB Is One Component of the Binding Complex of the Ces-2/E2A-HLF Binding Element and Is an Integral Part of the Interleukin-3 Survival Signal Mol. Cell. Biol., July 15, 2001; 21(14): 4636 - 4646. [Abstract] [Full Text] [PDF]

				S. E. Porter, L. D. Dwyer-Nield, and A. M. Malkinson Regulation of lung epithelial cell morphology by cAMP-dependent protein kinase type I isozyme Am J Physiol Lung Cell Mol Physiol, June 1, 2001; 280(6): L1282 - L1289. [Abstract] [Full Text] [PDF]

				N. H. Woo, S. N. Duffy, T. Abel, and P. V. Nguyen Genetic and Pharmacological Demonstration of Differential Recruitment of cAMP-Dependent Protein Kinases by Synaptic Activity J Neurophysiol, December 1, 2000; 84(6): 2739 - 2745. [Abstract] [Full Text] [PDF]

				E. A. Gangolli, M. Belyamani, S. Muchinsky, A. Narula, K. A. Burton, G. S. McKnight, M. D. Uhler, and R. L. Idzerda Deficient Gene Expression in Protein Kinase Inhibitor alpha Null Mutant Mice Mol. Cell. Biol., May 15, 2000; 20(10): 3442 - 3448. [Abstract] [Full Text]

				M. J. Barresi, H. L. Stickney, and S. H. Devoto The zebrafish slow-muscle-omitted gene product is required for Hedgehog signal transduction and the development of slow muscle identity Development, May 15, 2000; 127(10): 2189 - 2199. [Abstract] [PDF]

				T. E. Thiele, B. Willis, J. Stadler, J. G. Reynolds, I. L. Bernstein, and G. S. McKnight High Ethanol Consumption and Low Sensitivity to Ethanol-Induced Sedation in Protein Kinase A-Mutant Mice J. Neurosci., May 15, 2000; 20(10): RC75 - RC75. [Abstract] [Full Text] [PDF]

				M. E. Cox, P. D. Deeble, E. A. Bissonette, and S. J. Parsons Activated 3',5'-Cyclic AMP-dependent Protein Kinase Is Sufficient to Induce Neuroendocrine-like Differentiation of the LNCaP Prostate Tumor Cell Line J. Biol. Chem., April 28, 2000; 275(18): 13812 - 13818. [Abstract] [Full Text] [PDF]

				J.-P. Pursiheimo, M. Jalkanen, K. Tasken, and P. Jaakkola Involvement of protein kinase A in fibroblast growth factor-2-activated transcription PNAS, January 4, 2000; 97(1): 168 - 173. [Abstract] [Full Text] [PDF]

				J. V. Planas, D. E. Cummings, R. L. Idzerda, and G. S. McKnight Mutation of the RIIbeta Subunit of Protein Kinase A Differentially Affects Lipolysis but Not Gene Induction in White Adipose Tissue J. Biol. Chem., December 17, 1999; 274(51): 36281 - 36287. [Abstract] [Full Text] [PDF]

				H. Zhao, M. R. Wiederkehr, L. Fan, R. L. Collazo, L. A. Crowder, and O. W. Moe Acute Inhibition of Na/H Exchanger NHE-3 by cAMP. ROLE OF PROTEIN KINASE A AND NHE-3 PHOSPHOSERINES 552 AND 605 J. Biol. Chem., February 12, 1999; 274(7): 3978 - 3987. [Abstract] [Full Text] [PDF]

				A Ruiz i Altaba Gli proteins encode context-dependent positive and negative functions: implications for development and disease Development, January 6, 1999; 126(14): 3205 - 3216. [Abstract] [PDF]

				M. J. Smit, D. Verzijl, and R. Iyengar Identity of adenylyl cyclase isoform determines the rate of cell cycle progression in NIH 3T3 cells PNAS, December 8, 1998; 95(25): 15084 - 15089. [Abstract] [Full Text] [PDF]

				E. Lalli, M. H. Melner, D. M. Stocco, and P. Sassone-Corsi DAX-1 Blocks Steroid Production at Multiple Levels Endocrinology, October 1, 1998; 139(10): 4237 - 4243. [Abstract] [Full Text] [PDF]

				J. J. Watters and D. M. Dorsa Transcriptional Effects of Estrogen on Neuronal Neurotensin Gene Expression Involve cAMP/Protein Kinase A-Dependent Signaling Mechanisms J. Neurosci., September 1, 1998; 18(17): 6672 - 6680. [Abstract] [Full Text] [PDF]

				P. A. Witt-Enderby, M. I. Masana, and M. L. Dubocovich Physiological Exposure to Melatonin Supersensitizes the Cyclic Adenosine 3',5'-Monophosphate-Dependent Signal Transduction Cascade in Chinese Hamster Ovary Cells Expressing the Human mt1 Melatonin Receptor Endocrinology, July 1, 1998; 139(7): 3064 - 3071. [Abstract] [Full Text] [PDF]

				E. P. Brandon, S. F. Logue, M. R. Adams, M. Qi, S. P. Sullivan, A. M. Matsumoto, D. M. Dorsa, J. M. Wehner, G. S. McKnight, and R. L. Idzerda Defective Motor Behavior and Neural Gene Expression in RIIbeta -Protein Kinase A Mutant Mice J. Neurosci., May 15, 1998; 18(10): 3639 - 3649. [Abstract] [Full Text] [PDF]

				C. R. Guthrie, B. S. Skalhegg, and G. S. McKnight Two Novel Brain-specific Splice Variants of the Murine Cbeta Gene of cAMP-dependent Protein Kinase J. Biol. Chem., November 21, 1997; 272(47): 29560 - 29565. [Abstract] [Full Text] [PDF]

				M. R. Adams, E. P. Brandon, E. H. Chartoff, R. L. Idzerda, D. M. Dorsa, and G. S. McKnight Loss of haloperidol induced gene expression and catalepsy in protein kinase A-deficient mice PNAS, October 28, 1997; 94(22): 12157 - 12161. [Abstract] [Full Text] [PDF]

				K. A. Burton, B. D. Johnson, Z. E. Hausken, R. E. Westenbroek, R. L. Idzerda, T. Scheuer, J. D. Scott, W. A. Catterall, and G. S. McKnight Type II regulatory subunits are not required for the anchoring-dependent modulation of Ca2+ channel activity by cAMP-dependent protein kinase PNAS, September 30, 1997; 94(20): 11067 - 11072. [Abstract] [Full Text] [PDF]

				M. Lamas and P. Sassone-Corsi The Dynamics of the Transcriptional Response to Cyclic Adenosine 3',5'-Monophosphate: Recurrent Inducibility and Refractory Phase Mol. Endocrinol., September 1, 1997; 11(10): 1415 - 1424. [Abstract] [Full Text]

				R. Bernabeu, L. Bevilaqua, P. Ardenghi, E. Bromberg, P. Schmitz, M. Bianchin, I. Izquierdo, and J. H. Medina Involvement of hippocampal cAMP/cAMP-dependent protein kinase signaling pathways in a late memory consolidation phase of aversively motivated learning in rats PNAS, June 24, 1997; 94(13): 7041 - 7046. [Abstract] [Full Text] [PDF]

				P. S. Amieux, D. E. Cummings, K. Motamed, E. P. Brandon, L. A. Wailes, K. Le, R. L. Idzerda, and G. S. McKnight Compensatory Regulation of RIalpha Protein Levels in Protein Kinase A Mutant Mice J. Biol. Chem., February 14, 1997; 272(7): 3993 - 3998. [Abstract] [Full Text] [PDF]

				W. J. Wolfgang, I. J. H. Roberts, F. Quan, C. O'Kane, and M. Forte Activation of protein kinase A-independent pathways by Gsalpha in Drosophila PNAS, December 10, 1996; 93(25): 14542 - 14547. [Abstract] [Full Text] [PDF]

				M Hammerschmidt, M J Bitgood, and A P McMahon Protein kinase A is a common negative regulator of Hedgehog signaling in the vertebrate embryo. Genes & Dev., March 15, 1996; 10(6): 647 - 658. [Abstract] [PDF]

				J Chen and R Iyengar Suppression of Ras-induced transformation of NIH 3T3 cells by activated G alpha s Science, March 4, 1994; 263(5151): 1278 - 1281. [Abstract] [PDF]

				R Numann, W. Catterall, and T Scheuer Functional modulation of brain sodium channels by protein kinase C phosphorylation Science, October 4, 1991; 254(5028): 115 - 118. [Abstract] [PDF]

				R A Firtel and A L Chapman A role for cAMP-dependent protein kinase A in early Dictyostelium development. Genes & Dev., January 1, 1990; 4(1): 18 - 28. [Abstract] [PDF]

				D Kalderon and G M Rubin Isolation and characterization of Drosophila cAMP-dependent protein kinase genes. Genes & Dev., December 1, 1988; 2(12a): 1539 - 1556. [Abstract] [PDF]

				S. A. Orellana and C. Marfella-Scivittaro Distinctive Cyclic AMP-dependent Protein Kinase Subunit Localization Is Associated with Cyst Formation and Loss of Tubulogenic Capacity in Madin-Darby Canine Kidney Cell Clones J. Biol. Chem., July 7, 2000; 275(28): 21233 - 21240. [Abstract] [Full Text] [PDF]

				M. C. Hu, L. Fan, L. A. Crowder, Z. Karim-Jimenez, H. Murer, and O. W. Moe Dopamine Acutely Stimulates Na+/H+ Exchanger (NHE3) Endocytosis via Clathrin-coated Vesicles. DEPENDENCE ON PROTEIN KINASE A-MEDIATED NHE3 PHOSPHORYLATION J. Biol. Chem., July 13, 2001; 276(29): 26906 - 26915. [Abstract] [Full Text] [PDF]

				E. A. Vitalis, J. L. Costantin, P.-S. Tsai, H. Sakakibara, S. Paruthiyil, T. Iiri, J.-F. Martini, M. Taga, A. L. H. Choi, A. C. Charles, et al. Role of the cAMP signaling pathway in the regulation of gonadotropin-releasing hormone secretion in GT1 cells PNAS, February 15, 2000; 97(4): 1861 - 1866. [Abstract] [Full Text] [PDF]

				C. Marfella-Scivittaro, A. Quinones, and S. A. Orellana cAMP-dependent protein kinase and proliferation differ in normal and polycystic kidney epithelia Am J Physiol Cell Physiol, April 1, 2002; 282(4): C693 - C707. [Abstract] [Full Text] [PDF]