Skip to main content
SpringerLink
Log in

Cyclic AMP-Dependent Protein Phosphorylation

  • Chapter
Cyclic Nucleotides

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 58 / 1))

Overview

Since the early findings that most if not all effects of cAMP are mediated via its binding to the regulatory subunit of cAMP-dependent protein kinase, a considerable amount of effort has been expended delineating the mechanism(s) by which cAMP activates protein kinase and what the functions of the active kinase are in the cell. Some of the more important general observations can be summarized as follows. Two major types of cAMP-dependent protein kinase are known; both types exist as asymetric tetramers composed of two catalytic subunits (C) and one dimeric regulatory subunit (R2). Upon exposure to a saturating dose of cAMP a three species complex of cAMP, regulatory and catalytic subunit is formed. At what are probably physiological concentrations of enzyme, this complex dissociates into two free, active catalytic subunits and one R dimer having 4 cyclic AMP molecules bound. The Kd of the R: C interaction for either major isozyme type appears to be about 0.5 nM. The association and dissociation rates are probably fast enough at physiological enzyme concentrations to allow protein kinase to mediate rapidly oscillating processes in vivo.

Once activated, the enzyme is capable of promoting the phosphorylation of a large number of proteins in vitro. However, current data indicates that many of these substrates are probably not physiologically important. This chapter presents a number of criteria which are useful in determining if cyclic nucleotide-dependent phosphorylations are meaningful in vivo events. It also discusses the types of changes in enzyme function usually caused by phosphorylation. A number of relatively new physiologically important substrates for cAMP-dependent protein kinase are also described. These include myosin light chain kinase, the src gene product, calmodulin-dependent cyclic nucleotide phosphodiesterase and ATP citrate lyase. Of these, only the light chain kinase has as yet been shown to be regulated both in vitro and in vivo by cAMP-dependent phosphorylation.

In addition to research on the substrates of cAMP-dependent protein kinase, this chapter describes current research on the regulation, physiology and possible differential function of the two major isozymes of this enzyme. Numerous studies have shown that protein kinase is compartmentalized within the cell and that the function of an isozyme may be regulated by its location. Protein kinase also appears to be translocated between cellular compartments during treatment of certain cells with agents that raise intracellular cAMP levels. The use of mutants with altered protein kinase has led to an understanding of the role of the enzyme in regulation of processes, such as cell growth, which do not lend themselves to simple biochemical analysis. Studies on the regulation of the amounts of regulatory and catalytic subunits have indicated that while in most tissues both subunits are present in stoichiometric amounts, certain cell types appear to differentially regulate R and C.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adelstein RS, Eisenberg E (1980) Regulation and kinetics of the actin-myosin-ATP interaction. Ann Rev Biochem 49:921–956

    Article  PubMed  CAS  Google Scholar 

  • Adelstein RS, Conti MA, Hathaway DR, Klee CR (1978) Phosphorylation of smooth muscle myosin light chain kinase by the catalytic subunit of adenosine 3′:5′-monophosphate-dependent protein kinase. J Biol Chem 253:8347–8350

    PubMed  CAS  Google Scholar 

  • Ames MM, Lerner P, Lovenberg W (1978) Tyrosine hydroxylase, activation by protein phosphorylation and end product inhibition. J Biol Chem 253:27–31

    PubMed  CAS  Google Scholar 

  • Beale EG, Dedman JR, Means AR (1977) Isolation and characterization of a protein from rat testis which inhibits cyclic AMP-dependent protein kinase and phosphodiesterase. J Biol Chem 252:6322–6327

    PubMed  CAS  Google Scholar 

  • Beavo JA, Bechtel PJ, Krebs EG (1974) Activation of protein kinase by physiological concentrations of cyclic AMP. Proc Natl Acad Sci USA 71:3580–3583

    Article  PubMed  CAS  Google Scholar 

  • Beavo JA, Bechtel PJ, Krebs EG (1974 a) Preparation of homogeneous cyclic AMP-dependent protein kinase(s) and its subunits from rabbit skeletal muscle. Methods Enzymol 38:299–308

    Article  PubMed  CAS  Google Scholar 

  • Beavo JA, Bechtel PJ, Krebs EG (1975) Mechanisms of control for cyclic AMP dependent protein kinase from skeletal muscle. Adv Cyclic Nucleotide Res 5:241–251

    PubMed  CAS  Google Scholar 

  • Bechtel PJ, Beavo JA, Krebs EG (1977) Purification and characterization of catalytic subunit of skeletal muscle adenosine 3′,5′-monophosphate-dependent protein kinase. J Biol Chem 252:2691–2697

    PubMed  CAS  Google Scholar 

  • Beg ZH, Allmann DW, Gibson DM (1973) Modulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity with cAMP and with protein fractions of rat liver cytosol. Biochem Biophys Res Commun 54:1362–1369

    Article  PubMed  CAS  Google Scholar 

  • Blat C, Loeb JE (1971) Effect of glucagon on phosphorylation of some rat liver ribosomal proteins in vivo. FEBS Lett 18:124–126

    Article  PubMed  CAS  Google Scholar 

  • Brand IA, Soling HD (1975) Activation and inactivation of rat liver phosphofructokinase by phosphorylation-dephosphorylation. FEBS Lett 57:163–168

    Article  PubMed  CAS  Google Scholar 

  • Brostrom MA, Reimann EM, Walsh DA, Krebs EG (1970) Cyclic 3′,5′-AMP stimulated protein kinase from cardiac muscle. Adv Enzyme Reg 8:191–203

    Article  CAS  Google Scholar 

  • Builder SE, Beavo JA, Krebs EG (1980) Stoichiometry of cAMP and l, N6-etheno-cAMP binding to protein kinase. J Biol Chem 255:2350–2354

    PubMed  CAS  Google Scholar 

  • Builder SE, Beavo JA, Krebs EG (1980 a) The mechanism of activation of bovine skeletal muscle protein kinase by adenosine 3′:5′ monophosphate. J Biol Chem 255:3514–3519

    PubMed  CAS  Google Scholar 

  • Bylund DB, Krebs EG (1975) Effect of denaturation on the susceptibility of proteins to enzymic phosphorylation. J Biol Chem 250:6355–6361

    PubMed  CAS  Google Scholar 

  • Carlson CA, Kim KH (1973) Regulation of hepatic acetyl coenzyme A carboxylase by phosphorylation and dephosporylation. J Biol Chem 248:378–380

    PubMed  CAS  Google Scholar 

  • Carlson GM, Bechtel PJ, Graves DJ (1980) Chemical and regulatory properties of phosporylase kinase and cAMP dependent protein kinase. Adv Enzymol 50:41–115

    Google Scholar 

  • Castagna M, Palmer WR, Walsh DA (1975) Nuclear protein kinase activity in perfused rat liver stimulated with dibutyryl-adenosine cyclic 3′:5′-monophosphate. Eur J Biochem 55:193–199

    Article  PubMed  CAS  Google Scholar 

  • Chau V, Huang LC, Romero G, Biltonen RL, Huana C (1980) Kinetic studies on the dissociation of adenosine cyclic 3′,5′-monophosphate from the regulatory subunit from rabbit skeletal muscle. Biochemistry 19:924–928

    Article  PubMed  CAS  Google Scholar 

  • Chen LJ, Walsh DA (1971) Multiple forms of hepatic adenosine 3′:5′-monophosphate dependent protein kinase. Biochemistry 10:3614–3620

    Article  PubMed  CAS  Google Scholar 

  • Cho-Chung YS, Clair T, Porper R (1977) Cyclic AMP-binding proteins and protein kinase during regression of Walker 256 mammary carcinoma. J Biol Chem 252:6342–6348

    PubMed  CAS  Google Scholar 

  • Coffino P, Bourne HR, Friedrich U, Hochman J, Insel PA, Lemaire I, Melmon KL, Tom-kins GM (1976) Molecular mechanisms of cylcic AMP action: A genetic approach. Rec Prog Hormones Res 32:669–684

    CAS  Google Scholar 

  • Cohen P (1978) The role of cyclic AMP-dependent protein kinase in the regulation of glycogen metabolism in mammalian skeletal muscle. Curr Top Cell Reg 14:118–196

    Google Scholar 

  • Cole HA, Perry SV (1975) The phosphorylation of troponin I from cardiac muscle. Biochem J 149:525–533

    PubMed  CAS  Google Scholar 

  • Collett MS, Erickson E, Erickson RL (1979) Structural analysis of the avian sarcoma virus transforming protein: sites of phosphorylation. J Virol 29:770–781

    PubMed  CAS  Google Scholar 

  • Corbin JD, Keely SL (1976) Characterization and regulation of heart adenosine 3′,5′ mono-phosphate-dependent protein kinase isozymes. J Biol Chem 252:910–918

    Google Scholar 

  • Corbin JD, Keely SL, Park CR (1975) The distribution and dissociation of cyclic adenosine 3′,5′-monophosphate-dependent protein kinases in adipose, cardiac, and other tissues. J Biol Chem 250:218–225

    PubMed  CAS  Google Scholar 

  • Corbin JD, Sugden PH, Lincoln TM, Keely SL (1977) Compartmentalization of adenosine 3′,5′-monophosphate and adenosine 3′,5′-monophosphate-dependent protein kinase in heart tissue. J Biol Chem 252:3854–3861

    PubMed  CAS  Google Scholar 

  • Corbin JD, Sugden PH, West L, Flockhart DA, Lincoln TM, McCarthy D (1978) Studies on the properties and mode of action of the purified regulatory subunit of bovine heart adenosine 3′,5′ monophosphate dependent protein kinase. J Biol Chem 253:3997–4003

    PubMed  CAS  Google Scholar 

  • Costa E, Kurosawa A, Guidotti A (1976) Activation and nuclear translocation of protein kinase during transsynaptic induction of tyrosine 3-monooxygenase. Proc Natl Acad Sci USA 73:1058–1062

    Article  PubMed  CAS  Google Scholar 

  • DeMaille JG, Peters KA, Fischer EH (1977) Isolation and properties of the rabbit skeletal muscle inhibitor of adenosine 3′,5′ monophosphate dependent protein kinases. Biochemistry 16:3080–3086

    Article  PubMed  CAS  Google Scholar 

  • Dills WL, Beavo JA, Bechtel PJ, Krebs EG (1975) Purification of rabbit skeletal muscle protein kinase regulatory subunit using cyclic adenosine 3′,5′ monophosphate affinity chro-matography. Biochem Biophys Res Commun 62:70–77

    Article  PubMed  CAS  Google Scholar 

  • Dills WL, Goodwin CO, Lincoln TM, Beavo JA, Bechtel PJ, Corbin JD, Krebs EG (1978) Purification of cyclic nucleotide receptor proteins by cyclic nucleotide affinity chroma-tography. Adv Cyclic Nucleotide Res 10:199–217

    Google Scholar 

  • Donlon J, Kaufman S (1978) Glucagon stimulation of rat hepatic phenyl adenosine hydroxylase through phosphorylation in vivo. J Biol Chem 253:6657–6659

    PubMed  CAS  Google Scholar 

  • Eldik LJV, Watterson DM (1979) Phosphorylation and calmodulin stimulated activities. Fed Proc 38:789

    Google Scholar 

  • Engstrom L (1978) The regulation of liver pyruvate kinase by phosphorylation-dephosphorylation. Curr Top Cell Regul 13:29–51

    CAS  Google Scholar 

  • Erlichman J, Rosenfeld R, Rosen OM (1974) Phosphorylation of a cyclic adenosine 3′,5′-monophosphate-dependent protein kinase from bovine cardiac muscle. J Biol Chem 249:5000–5003

    PubMed  CAS  Google Scholar 

  • Erlichman J, Sarkar D, Fleischer N, Rubin CW (1980) Identification of two subclasses of type II cAMP dependent protein kinases: Neural specific and non-neural protein kinases. J Biol Chem 256:8179–8184

    Google Scholar 

  • Evain D, Gottesman M, Pastan I, Anderson WB (1979) A mutation affecting the catalytic subunit of cyclic AMP-dependent protein kinase in CHO cells. J Biol Chem 254:6931–6937

    PubMed  CAS  Google Scholar 

  • Fischer EH, Heilmeyer LMG, Haschke RH (1971) Phosphorylase and the control of glycogen degradation. Curr Top Cell Regul 4:211–251

    CAS  Google Scholar 

  • Friedman DL, Larner J (1963) Studies on UDPG-x-glucan transglycosylase III. Interconversion of two forms of muscle UDPG-x-glucan transglycosylase by a phosphorylation-dephosphorylation reaction sequence. Biochemistry 2:669–675

    Article  PubMed  CAS  Google Scholar 

  • Gabibov AG, Kochetkov SN, Sashchenko LP, Severin ES (1979) Biochim Biophys Acta 569:445–452

    Google Scholar 

  • Geahlen RL, Krebs EG (1980 a) Regulatory subunit of the type I cAMP dependent protein kinase as an inhibitor and substrate of the cGMP-dependent protein kinase. J Biol Chem 255:1164–1169

    PubMed  CAS  Google Scholar 

  • Geahlen RL, Krebs EG (1980 b) Studies on the phorphorylation of the type I cAMP dependent protein kinase. J Biol Chem 255:9375–9379

    PubMed  CAS  Google Scholar 

  • Geahlen RL, Allen SM, Krebs EG (1981) Effect of phosphorylation on the regulatory subunit of the type I cAMP-dependent protein kinase. J Biol Chem 256:4536–4540

    PubMed  CAS  Google Scholar 

  • Gibson DM, Ingebritsen TS (1978) Reversible modulation of liver hydroxymethyl glutaryl CoA reductase. Life Sci 23:2649–2664

    Article  PubMed  CAS  Google Scholar 

  • Gill GN, Garren ID (1971) Role of the receptor in the mechanism of adenosine 3′,5′-cyclic monophosphate, Proc Natl Acad Sci USA 68:786–790

    Article  PubMed  CAS  Google Scholar 

  • Greaser ML, Gergely J (1971) Reconstitution of troponin activity from three protein components. J Biol Chem 246:4226–4233

    PubMed  CAS  Google Scholar 

  • Gressner AM, Wool IG (1976) Influence of glucagon and cyclic adenosine 3′:5′-monophosphate on the phosphorylation of rat liver ribosomal protein S 6. J Biol Chem 251:1500–1504

    PubMed  CAS  Google Scholar 

  • Gutmann MS, Rae PA, Schimmer BP (1978) Altered cyclic AMP-dependent protein kinase activity in a mutant adrenocortical tumor cell line. J Cell Physiol 97:451–460

    Article  PubMed  CAS  Google Scholar 

  • Guy PS, Cohen P, Hardie DG (1980) Rat mammary gland ATP-citrate lyase is phosphorylated by cyclic AMP-dependent protein kinase. FEBS Lett 109:205–208

    Article  PubMed  CAS  Google Scholar 

  • Haddox MK, Newton NE, Hartle DK, Goldberg ND (1972) ATP (Mg2+) induced inhibition of cyclic AMP reactivity with a skeletal muscle protein kinase. Biochem Biophys Res Commun 47:653–661

    Article  PubMed  CAS  Google Scholar 

  • Hamon M, Bourgoin S, Artasud F, Hery F (1977) Rat brain stem tryptophan hydroxylase: mechanism of activation by calcium. J Neurochem 28:811–818

    Article  PubMed  CAS  Google Scholar 

  • Hardie DG, Cohen P (1978) The regulation of fatty acid biosynthesis: Simple procedure for the purification of acetyl CoA carboxylase from lactating rabbit mammary gland, and its phosphorylation by endogenous cyclic AMP-dependent and-independent protein kinase activities. FEBS Lett 91:1–7

    Article  PubMed  CAS  Google Scholar 

  • Hochman J, Insel PA, Bourne HR, Coffino P, Tomkins GM (1975) A structural gene mutation affecting the regulatory subunit of cyclic AMP-dependent protein kinase in mouse lymphoma cells. Proc Natl Acad Sci USA 72:5051–5055

    Article  PubMed  CAS  Google Scholar 

  • Hofmann F, Beavo JA, Bechtel PJ, Krebs EG (1975) Comparison of adenosine 3′,5′-cyclic monophosphate-dependent protein kinases from rabbit skeletal and bovine heart muscle. J Biol Chem 250:7795–7801

    PubMed  CAS  Google Scholar 

  • Hofmann F, Bechtel PJ, Krebs EG (1977) Concentrations of cyclic AMP-dependent protein kinase subunits in various tissues. J Biol Chem 252:1441–1447

    PubMed  CAS  Google Scholar 

  • Hollenbeck RA, Chuang DM, Costa E (1979) Translocation of cytosol protein kinase into nuclei and the induction of tyrosine hydroxylase in NBD-2 neuroblastoma cells. Brain Res 171:481–487

    Article  PubMed  CAS  Google Scholar 

  • Hoppe J, Freist W (1979) Localization of the high-affinity ATP site in adenosine 3′:5′-dependent protein kinase type I. Eur J Biochem 93:141–146

    Article  PubMed  CAS  Google Scholar 

  • Hoppe J, Marutzky R, Freist W, Wagner KG (1977) Mechanism of activation of the protein kinase I from rabbit skeletal muscle. Eur J Biochem 80:369–372

    Article  PubMed  CAS  Google Scholar 

  • Hoppe J, Wagner KG (1977) An improved method for the purification of cAMP-dependent protein kinase from rabbit muscle using hydrophobic chromatography. Febs Lett 74:95–98

    Article  PubMed  CAS  Google Scholar 

  • Huang FL, Glinsman WH (1975) Inactivation of rabbit muscle phosphorylase phosphatase by cyclic AMP-dependent kinase. Proc Natl Acad Sci USA 72:3004–3008

    Article  PubMed  CAS  Google Scholar 

  • Huang TS, Feramisco JR, Glass DB, Krebs EG (1979) Specificity consideration relevant to protein kinase activation and function. Miami Winter Symposia, vol 16, pp 449–461

    CAS  Google Scholar 

  • Hunter T, Sefton BM (1980) Transforming gene product of rous sarcoma virus phosphorylates tyrosine. Proc Natl Acad Sci USA 77:1311–1315

    Article  PubMed  CAS  Google Scholar 

  • Insel PA, Bourne HR, Coffmo P, Tomkins GM (1975) Cyclic AMP-dependent protein kinase: Pivotal role in regulation of enzyme induction and growth. Science 190:896–898

    Article  PubMed  CAS  Google Scholar 

  • Insel PA, Fenno J (1978) Cyclic AMP-dependent protein kinase mediates a cyclic AMP-stimulated decrease in ornithine and S-adenosyl methionine decarboxylase activities. Proc Natl Acad Sci USA 75:862–865

    Article  PubMed  CAS  Google Scholar 

  • Janski AM, Srere PA, Cornell NW, Veech RL (1979) Phosphorylation of ATP citrate lyase in response to glucogen. J Biol Chem 254:9365–9368

    PubMed  CAS  Google Scholar 

  • Jungmann RA, Hiestand PC, Schweppe JS (1974) Mechanism of action of gonadotropin. IV. Cyclic adenosine monophosphate-dependent translocation of ovarian cytoplasmic cyclic adenosine monophosphate-binding protein and protein kinase to nuclear acceptor sites. Endocrinology 94:168–183

    Article  PubMed  CAS  Google Scholar 

  • Jungmann RA, Lee SG, DeAngelo AB (1975) Translocation of cytoplasmic protein kinase and cyclic adenosine monophosphate binding protein to intracellular acceptor sites. Adv Cyclic Nucleotide Res 5:281–306

    PubMed  CAS  Google Scholar 

  • Jungmann RA, Christensen ML, Schweppe JS, Mednicks MI, Spielvogel AM (1976) Cyclic AMP-mediated nuclear translocation of cytoplasmic cAMP-dependent protein kinases: Identity of the nuclear and cytoplasmic enzymes. In: Cyclic nucleotides and the regulation of cell growth. Dowden, Hutchinson and Ross, Stroudsburg, pp 225–252

    Google Scholar 

  • Jungman RA, Russell DH (1977) Cyclic AMP, cyclic AMP-dependent protein kinase, and the regulation of gene expression. Life Sci 20:1787–1798

    Article  Google Scholar 

  • Keely SL, Corbin JD, Park CR (1975) On the question of translocation of heart cAMP-dependent protein kinase. Proc Natl Acad Sci USA 72:1501–1504

    Article  PubMed  CAS  Google Scholar 

  • Kemp BE, Bylund DV, Huang TS, Krebs EG (1975) Substrate specificity of the cyclic AMP-dependent protein kinase. Proc Natl Acad Sci USA 72:3448–3452

    Article  PubMed  CAS  Google Scholar 

  • Kemp BE, Graves DJ, Benjamini E, Krebs EG (1977) Role of multiple basic residues in determining the substrate specificity of cyclic AMP-dependent protein kinase. J Biol Chem 252:4888–4894

    PubMed  CAS  Google Scholar 

  • Khoo JC, Steinberg D, Huang JJ, Vagelos PR (1976) Triglyceride, diglyceride, monogly-ceride, and cholesterol ester hydrolases in chicken adipose tissue activated by adenosine 3′,5′ monophosphate dependent protein kinase. J Biol Chem 251:2882–2890

    PubMed  CAS  Google Scholar 

  • Krebs EG (1973) The mechanism of hormonal regulation by cyclic AMP. In: Endocrinology proceedings of the 4 th international congress. Excerpta Medica, Amsterdam, pp 17–29

    Google Scholar 

  • Krebs EG, Graves DJ, Fischer E (1959) Factors affecting the activity of muscle phosphorylase b kinase. J Biol Chem 234:2867–2873

    PubMed  CAS  Google Scholar 

  • Krebs EG, Beavo JA (1979) Phosphorylation-dephosphorylation of enzymes. Ann Rev Biochem 48:923–959

    Article  PubMed  CAS  Google Scholar 

  • Kurosawa A, Guidotti A, Costa E (1976) Induction of tyrosine 3-monooxygenase elicited by carbamylcholine in intact and denervated adrenal medulla: Role of protein kinase activation and translocation. Mol Pharmacol 12:420–432

    PubMed  CAS  Google Scholar 

  • Langan TA (1968) Histone phosphorylation: Stimulation by adenosine 3′,5′-monophosphate. Science 162:579–581

    Article  PubMed  CAS  Google Scholar 

  • LaPorte DC, Builder SE, Storm DR (1980) Spectroscopic studies of the cAMP binding sites of the regulatory subunits of types I and II protein kinase. J Biol Chem 255:2343–2349

    PubMed  CAS  Google Scholar 

  • Linn TC, Srere PA (1978) Identification of ATP citrate lyase a phosphoprotein. J Biol Chem 254:1691–1698

    Google Scholar 

  • Ljungstrom O, Hjelmquist G, Engstrom L (1974) Phosphorylation of purified rat liver pyruvate kinase by cyclic 3′,5′-AMP-stimulated protein kinase. Biochim Biophys Acta 358:289–298

    Google Scholar 

  • Lohmann SM, Walter U, Greengard P (1978) Protein kinases in developing rat brain. J Cyclic Nucleotide Res 4:445–452

    PubMed  CAS  Google Scholar 

  • Manning DR, DiSalvo J, Stull JT (1980) Protein phosphorylation: Quantitative analysis in vivo and in intact cell systems. Mol Cell Endocrinol 19:1–19

    Article  PubMed  CAS  Google Scholar 

  • McPherson JM, Whitehouse S, Walsh DA (1979) Possibility of shape conformers of the protein inhibitor of the cyclic adenosine monophosphate-dependent protein kinase. Biochemistry 18:4835–4845

    Article  PubMed  CAS  Google Scholar 

  • Mendicino J, Beaudreau C, Bhattacharyya RN (1966) Reversible inactivation of D-fructose 1,6-diphosphatase by adenosine triphosphate and cyclic 3′,5′-adenosine monophos-phate. Arch Biochem Biophys 116:436–445

    Article  PubMed  CAS  Google Scholar 

  • Miyamoto E, Petzold GL, Kuo JF, Greengard P (1973) Dissociation and activation of adenosine 3′,5′ monophosphate dependent and guanosine 3′,5′ monophosphate dependent protein kinases by cyclic nucleotides and by substrate protein. J Biol Chem 248:179–189

    PubMed  CAS  Google Scholar 

  • Miyamoto E, Petzold GL, Harris JS, Greengard P (1971) Dissociation and concomitant activation of adenosine 3′,5′ monophosphate dependent protein kinase by histone. Biochem Biophys Res Commun 44:305–312

    Article  PubMed  CAS  Google Scholar 

  • Milstein S, Abita SP, Chang N, Kaufman S (1976) Hepatic phenylalanine 4-monooxygenase is a phosphoprotein. Proc Natl Acad Sci USA 73:1591–1593

    Article  Google Scholar 

  • Morgenroth VH III, Hegstrand LR, Roth RH, Greengard P (1975) Evidence for involvement of protein kinase in the activation by adenosine 3′,5′-monophosphate of brain tyrosine 3-monooxygenase. J Biol Chem 250:1946–1948

    PubMed  CAS  Google Scholar 

  • Nimmo HG, Cohen P (1977) Hormonal control of cAMP dependent protein kinase. Adv Cyclic Nucleotide Res 8:145–266

    PubMed  CAS  Google Scholar 

  • Nimmo HG, Houston B (1978) Rat adipose-tissue glycerol phosphate acyltransferase can be inactivated by cyclic AMP-dependent protein kinase. Biochem J 176:607–610

    PubMed  CAS  Google Scholar 

  • O’Farrell PH (1975) High resolution two-dimensional electrophoresis of proteins. J Biol Chem 250:4007–4021

    PubMed  Google Scholar 

  • Ogez JR, Segel IH (1976) Interaction of cyclic adenosine 3′,5′ monophosphate with protein kinase: Equilibrium models. J Biol Chem 251:4551–4556

    PubMed  CAS  Google Scholar 

  • Owens JR, Haley BE (1978) Use of photo affinity analogs to determine the mechanism of ATP regulation of a membrane-bound cAMP-activated protein kinase. J Supra Mol Struct 9:57–68

    Article  CAS  Google Scholar 

  • Palmer WK, Castagna M, Walsh DA (1974) Nuclear protein kinase activity in glucagonstimulated perfused rat livers. Biochem J 142:469–471

    Google Scholar 

  • Palmer WK, McPherson JM, Walsh DA (1980) Critical controls in the evaluation of cAMP dependent protein kinase activity ratios as indices of hormonal action. J Biol Chem 255:2663–2666

    PubMed  CAS  Google Scholar 

  • Pilkus SJ, Pilkus J, Claus TH (1978) The effect of fructose diphosphate and phosphoenol pyruvate on cAMP-mediated inactivation of rat hepatic pyruvate kinase. Biochem Biophys Res Commun 81:139–146

    Article  Google Scholar 

  • Prasad N, Rosenberg RN (1978) Induction of cyclic AMP-binding proteins by ditbutyryl cyclic AMP in mouse neuroblastoma cells. Biochim Biophys Acta 539:459–469

    Article  Google Scholar 

  • Prasad N, Rosenberg RN, Wischmeyer B, Ulrich C, Sparkman D (1979) Induction of adenosine 3′,5′-monophosphate binding proteins by N6, O2-dibutyryladenosine 3′,5′-monophosphate in mouse neuroblastoma cells. Analysis by two-dimensional gel electrophoresis. Biochemistry 18:2717–2725

    Article  Google Scholar 

  • Rae PA, Gutmann NS, Tsao J, Schimmer BP (1979) Mutations in cyclic AMP-dependent protein kinase and corticopin (ACTH)-sensitive adenylate cyclase affect adrenal steroidogenesis. Proc Natl Acad Sci USA 76:1896–1900

    Article  PubMed  CAS  Google Scholar 

  • Ramakrishna S, Benjamin WB (1979) Fat cell protein phosphorylation identification of phosphoprotein 2 as ATP-citrate lyase. J Biol Chem 254:9232–9236

    PubMed  CAS  Google Scholar 

  • Ramseyer J, Kaslow JR, Gill GN (1974) Purification of the cAMP receptor protein by affinity chromatography. Biochem Biophys Res Commun 59:813–821

    Article  PubMed  CAS  Google Scholar 

  • Rangel-Aldao R, Kupiec JW, Rosen OM (1979) Resolution of the phosphorylated and dephosphorylated cAMP-binding proteins of bovine cardiac muscle by affinity labeling and two-dimensional electrophoresis. J Biol Chem 254:2499–2508

    PubMed  CAS  Google Scholar 

  • Rangel-Aldao R, Rosen OM (1976) Dissociation and reassociation of the phosphorylated and nonphosphorylated forms of adenosine 3′:5′-monophosphate-dependent protein kinase from bovine cardiac muscle. J Biol Chem 251:3375–3380

    PubMed  CAS  Google Scholar 

  • Rannels SR, Corbin JD (1980) Two intrachain cAMP binding sites of cAMP-dependent protein kinases. J Biol Chem 255:7085–7088

    PubMed  CAS  Google Scholar 

  • Reimann EM, Walsh DA, Krebs EG (1971) Purification and properties of rabbit skeletal muscle adenosine 3′,5′-monophosphate-dependent protein kinases. J Biol Chem 246:1986–1995

    PubMed  CAS  Google Scholar 

  • Riou JP, Claus TH, Flockhard DA, Corbin JD, Pilkis SJ (1977) In vivo and in vitro phosphorylation of rat liver fructose-1,6-bisphosphatase. Proc Natl Acad Sci USA 74:4615–4619

    Article  PubMed  CAS  Google Scholar 

  • Rizak MA (1964) Activation of an epinephrine-sensitive lipolytic activity from adipose tissue by adenosine 3′,5′-phosphate. J Biol Chem 239:392–395

    Google Scholar 

  • Rosell-Perez M, Larner J (1964) Studies on UDPG: 21.4 glucan x-4 glucosyltransferase. VI Specificity and structural requirements for the activator of the D form of the dog muscle enzyme. Biochemistry 3:773–778

    Article  PubMed  CAS  Google Scholar 

  • Rosen OM, Erlichman J, Rubin CS (1975) Molecular structure and characterization of bovine heart protein kinase. Adv Cyclic Nucleotide Res 5:253–263

    PubMed  CAS  Google Scholar 

  • Rosen OM, Erlichmann J (1975) Reversible autophosphorylation of a cyclic 3′,5′-AMP-dependent protein kinase from bovine cardiac muscle. J Biol Chem 250:7786–7794

    Google Scholar 

  • Rubin CS, Erlichmann J, Rosen OM (1974) Cyclic AMP-dependent protein kinase from bovine heart muscle. Methods Enzymol 38:299–308

    Article  Google Scholar 

  • Rubin CS, Rangel-Aldao R, Sarkar D, Erlichman J, Fleischer N (1979) Characterization and comparison of membrane-associated and cytosolic cAMP-dependent protein kinases. J Biol Chem 254:3797–3805

    PubMed  CAS  Google Scholar 

  • Schimmer BP, Rae PA, Gutmann NS, Watt VM, Tsao J (1979) Genetic dissection of ACTH action in adrenal tumor cells. Cold Spring Harbor Conf Cell Prolif 6:281–297

    CAS  Google Scholar 

  • Schwecheimer K, Hofmann F (1977) Properties of regulatory subunit of cAMP-dependent protein kinase (peak I) prepared by urea treatment of the holoenzyme. J Biol Chem 252:7690–7696

    Google Scholar 

  • Sefton BM, Hunter T, Beeman K (1980) Relationship of polypeptide products of the transforming gene of Rous sarcoma virus and the homologous gene of vertebrates. Proc Natl Acad Sci USA 77:2059–2063

    Article  PubMed  CAS  Google Scholar 

  • Sharma RK, Wang TH, Wirch E, Wang JH (1980) Purification and properties of bovine brain calmodulin dependent cyclic nucleotide phosphodiesterase. J Biol Chem 255:5916–5923

    PubMed  CAS  Google Scholar 

  • Simontov R, Sachs L (1975) Temperature sensitivity of cyclic adenosine 3′:5′-monophosphate-binding proteins and the regulation of growth and differentiation in neuroblastoma cells. J Biol Chem 250:3236–3242

    Google Scholar 

  • Smith CH, Brown NE, Larner J (1971) Glycogen synthesis II. Some chemical characteristics of the enzyme protein and of its change on interconversion. Biochim Biophys Acta 242:81–88

    PubMed  CAS  Google Scholar 

  • Smith SB, Siegel JB, Krebs EG (1980) Adenosine 3′,5′ monophosphate binding and tertiary structure changes in the regulatory subunit of protein kinase. Fed Proc 39:2117

    Google Scholar 

  • Soderling TR (1976) Regulation of glycogen synthetase: Effects of trypsin on the structure, activity, and phosphorylation of the skeletal muscle enzyme. J Biol Chem 251:4359–4364

    PubMed  CAS  Google Scholar 

  • Soderling TR (1979) Regulatory functions of protein multisite phosphorylation. Mol Cell Endocrinol 16:157–179

    Article  PubMed  CAS  Google Scholar 

  • Soderling TR, Hickenbottom JP, Reimann EM, Hunkeler FL, Walsh DA, Krebs EG (1970) Inactivation of glycogen synthetase and activation of phosphorylase kinase by muscle adenosine 3′,5′-monophosphate-dependent protein kinases. J Biol Chem 245:6317–6328

    PubMed  CAS  Google Scholar 

  • Spector M, O’Neal S, Racker E (1981) Regulation of phosphorylation of the β-subunit of the Ehrlich ascites tumor Na+K+-ATPase by a protein kinase cascade. J Biol Chem 256:4219–4227

    PubMed  CAS  Google Scholar 

  • Spruill WA, Steiner AL (1979) Cyclic nucleotide and protein kinase immunocytochemistry. Adv Cyclic Nucleotide Res 10:169–186

    PubMed  CAS  Google Scholar 

  • Steinberg D (1976) Interconvertible enzymes in adipose tissue regulated by cyclic AMP-dependent protein kinase. Adv Cyclic Nucleotide Res 7:157–198

    PubMed  CAS  Google Scholar 

  • Steinberg RA, Coffino P (1979) Two-dimensional gel analysis of cAMP effects in cultured S49 mouse lymphoma cells: Protein modifications, inductions, and repressions. Cell 18:719–733

    Article  PubMed  CAS  Google Scholar 

  • Steinberg RA, Wetters TV, Coffino P (1978) Kinase-negative mutants of S49 mouse lymphoma cells carry a trans-dominant mutation affecting expression of cAMP-dependent protein kinase. Cell 15:1351–1361

    Article  PubMed  CAS  Google Scholar 

  • Steinberg RA, O’Farrel PH, Frederick U, Coffino P (1977) Mutations causing charge alterations in regulatory subunits of the cAMP-dependent protein kinase of cultured S 49 lymphoma cells. Cell 10:381–391

    Article  PubMed  CAS  Google Scholar 

  • Stull JT (1980) Phosphorylation of contractile proteins in relation to muscle function. Adv Cyclic Nucleotide Res 13:39–93

    PubMed  CAS  Google Scholar 

  • Sugden PH, Holladay LA, Reimann EM, Corbin JD (1976) Purification and characterization of the catalytic subunit of adenosine 3′,5′-cyclic monophosphate-dependent protein kinase from bovine liver. Biochem J 159:409–422

    PubMed  CAS  Google Scholar 

  • Swillens W, Van Cauter E, Dumont JE (1974) Protein kinase and cyclic 3′,5′-AMP: Significance of binding and activation constants. Biochim Biophys Acta 364:250–259

    PubMed  CAS  Google Scholar 

  • Tash JS, Dedman JR, Means AR (1979) Protein kinase inhibitor in sertoli cell-enriched rat testis. J Biol Chem 254:1241–1247

    PubMed  CAS  Google Scholar 

  • Tao M (1972) Dissociation of rabbit red blood cell cyclic AMP dependent protein kinase I by protamine. Biochem Biophys Res Commun 46:56–61

    Article  PubMed  CAS  Google Scholar 

  • Tao M, Salas MI, Lipmann F (1970) Mechanisms of activation by adenosine 3′:5′-cyclic monophosphate of a protein phosphokinase from rabbit reticulocytes. Proc Natl Acad Sci USA 67:408–414

    Article  PubMed  CAS  Google Scholar 

  • Tessmer F, Graves DJ (1973) The phosphorylase kinase reaction on a peptide derived from glycogen phosphorylase. Biochem Biophys Res Commun 50:1–7

    Article  PubMed  CAS  Google Scholar 

  • Trzeciak WH, Boyd GS (1974) Activation of cholesteryl esterase in bovine adrenal cortex. Eur J Biochem 46:201–207

    Article  PubMed  CAS  Google Scholar 

  • Uno I, Ueda T, Greengard P (1977) Adenosine 3′,5′-monophosphate-regulated phosphoprotein system of neuronal membranes. J Biol Chem 252:5164–5174

    PubMed  CAS  Google Scholar 

  • Walsh DA, Ashby CD (1973) Protein kinases: Aspects of their regulation and diversity. Recent Prog Horm Res 29:329–359

    PubMed  CAS  Google Scholar 

  • Walsh DA, Ashby CD, Gonzalez C, Calkins D, Fischer E, Krebs E (1971) Purification and characterization of a protein inhibitor of adenosine 3′,5′-monophosphate-dependent protein kinases. J Biol Chem 246:1977–1985

    PubMed  CAS  Google Scholar 

  • Walter U, Costa M, Breakefield XO, Greengard P (1979) Presence of free cyclic AMP receptor protein and regulation of its level by cyclic AMP in neuroblastoma-glioma hybrid cells. Proc Nat Acad Sci USA 76:3251–3255

    Article  PubMed  CAS  Google Scholar 

  • Yamamura H, Takeda M, Kumon A, Nishizuka Y (1970) Adenosine 3′,5′ cyclic-phosphatedependent and independent histone kinases from rat liver. Biochem Biophys Res Commun 40:675–682

    Article  PubMed  CAS  Google Scholar 

  • Zoller MJ, Kerlavage AR, Taylor SS (1979) Structural comparisons of cAMP dependent protein kinases I and II from porcine muscle. J Biol Chem 254:2408–2412.

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. J. A. Beavo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. C. Mumby
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Neuropharmacology Research Laboratory, Departments of Neurology and Pharmacology, Harvard Medical School, Massachusetts General Hospital, Boston, MA, 02114, USA

    J. A. Nathanson

  2. Biochemical Neuropharmacology Unit, NINCDS National Institutes of Health, Bethesda, MD, 20205, USA

    J. W. Kebabian

Rights and permissions

Reprints and permissions

Copyright information

© 1982 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Beavo, J.A., Mumby, M.C. (1982). Cyclic AMP-Dependent Protein Phosphorylation. In: Nathanson, J.A., Kebabian, J.W. (eds) Cyclic Nucleotides. Handbook of Experimental Pharmacology, vol 58 / 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-68111-0_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-68111-0_11

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-68113-4

  • Online ISBN: 978-3-642-68111-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation