Abstract
The work of Edwin Krebs and his colleagues over a number of years culminated in the discovery of a cyclic AMP-dependent protein kinase in skeletal muscle (Walsh et al. 1968). Moreover, Krebs and his group provided strong evidence to suggest that this cyclic AMP-dependent protein kinase was involved in mediating the effects of epinephrine in the regulation of carbohydrate metabolism in skeletal muscle. Upon the appearance of this important paper by Krebs and his colleagues, Drs. Miyamoto, Kuo and I looked for and found a cyclic AMP-dependent protein kinase in mammalian brain (Miyamoto et al. 1969). Of particular interest, our results indicated that this enzyme was present in high concentration in brain and that it was greatly enriched in those subcellular fractions containing synaptic material. These results suggested that cyclic AMP-dependent protein kinase in the brain might be involved not only in regulation of carbohydrate metabolism, but also in regulation of some of the molecular processes underlying synaptic transmission, and possibly of other physiological processes occurring in the nervous system as well. For these reasons we proposed the hypothesis (Kuo and Greengard 1969), shown in Fig. 1, that in various tissues the diverse effects of cyclic AMP, both metabolic and physiological, were achieved through regulating the activity of this one class of enzyme, cyclic AMP-dependent protein kinase. According to this hypothesis, the hormone in the endocrine system or the neurotransmitter in the nervous system activates an adenylate cyclase; the activated adenylate cyclase causes an increased conversion of ATP to cyclic AMP; the newly formed cyclic AMP activates a cyclic AMP-dependent protein kinase; the activated protein kinase causes the phosphorylation of a substrate protein, converting it from the dephospho-form to the phospho-form; the phosphorylated substrate, through one or more steps, leads to the metabolic or physiological response characteristic of the hormone or neurotransmitter in question.
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References
Carpenter G, King C, Jr, Cohen S (1978) Epidermal growth factor stimulates phosphorylation in membrane preparations in vitro. Nature 276:409–410
Carpenter G, King C, Jr, Cohen S (1979) Rapid enhancement of protein phosphorylation in A-431 cell membrane preparations by epidermal growth factor. J Biol Chem 254:4884–4891
Castellucci VF, Kandel ER, Schwartz JH, Wilson F, Nairn AC, Greengard P (1980) Intracellular injection of catalytic subunit of cyclic AMP-dependent protein kinase simulates facilitation of transmitter release underlying behavioral sensitization in Aplysia. Proc Natl Acad Sci USA 77:7492–7496
Cohen P, Burchell A, Foulkes JF, Cohen PTW, Vanaman TC, Nairn AC (1978) Identification of the Ca2+-dependent modulator protein as the fourth subunit of rabbit skeletal muscle phosphorylase kinase. FEBS Lett 92:287–293
Collett MS, Erikson RL (1978) Protein kinase activity associated with the avian sarcoma virus sre gene product. Proc Natl Acad Sci USA 75:2021–2024
Dabrowska R, Sherry JMF, Aromatorio DK, Hartshorne DJ (1978) Modulator protein as a component of the myosin light chain kinase from chicken gizzard. Biochemistry 17:253–258
Forn J, Greengard P (1976) Regulation by lipolytic and antilipolytic compounds of the phosphorylation of specific proteins in isolated intact fat cells. Arch Biochem Biophys 176:721–733
Greengard P (1978) Phosphorylated proteins as physiological effectors. Science 199:146–152
Greengard P (1981) Intracellular signals in the brain. In: The Harvey Lecture Series. Academic Press, New York, in press
Kaczmarek LK, Jennings KR, Strumwasser F, Nairn AC, Walter U, Wilson FD, Greengard P (1980) Microinjection of catalytic subunit of cAMP-dependent protein kinase enhances calcium action potentials of bag cell neurons in cell culture. Proc Natl Acad Sci USA 77:7487–7491
Kennedy MB, Greengard P (1981) Two calcium/calmodulin-dependent protein kinases, which are highly concentrated in brain, phosphorylate Protein I at distinct sites. Proc Natl Acad Sci USA 78:1293–1297
Krebs EG (1972) Protein kinases. Curr Top Cell Regul 5:99–133
Kuo JF, Greengard P (1969) Cyclic nucleotide-dependent protein kinases. IV. Widespread occurrence of adenosine 3′,5′-monophosphate-dependent protein kinase in various tissues and phyla of the animal kingdom. Proc Natl Acad Sci USA 64:1349–1355
Kuo JF, Wyatt GR, Greengard P (1971) Cyclic nucleotide-dependent protein kinases. IX. Partial purification and some properties of guanosine 3′,5′-monophosphate-dependent and adenosine 3′,5′-monophosphate-dependent protein kinases from various tissues and species of Arthropoda. J Biol Chem 246:7159–7167
Langan T (1980) Malignant transformation and protein phosphorylation. Nature 286:329–330
Lebleu B, Sen GC, Shaila S, Cabrer B, Lengyel P (1976) Interferon, double-stranded RNA, and protein phosphorylation. Proc Natl Acad Sci USA 73:3107–3111
Levinson AD, Oppermann H, Levintow L, Varmus HE, Bishop JM (1978) Evidence that the transforming gene of avian sarcoma virus encodes a protein kinase associated with a phosphoprotein. Cell 15:561–572
Liu AY-C, Greengard P (1974) Aldosterone-induced increase in protein phosphatase activity in toad bladder. Proc Natl Acad Sci USA 71:3869–3873
Liu AY-C, Greengard P (1976) Regulation by steroid hormones of phosphorylation of specific protein common to several target organs. Proc Natl Acad Sci USA 73:568–572
Miyamoto E, Kuo JF, Greengard P (1969) Cyclic nucleotide-dependent protein kinases. III. Purification and properties of adenosine 3′,5′-monophosphate-dependent protein kinase from bovine brain. J Biol Chem 244:6395–6402
Nimmo HG, Cohen P (1977) Hormonal control of protein phosphorylation. Adv Cyclic Nucleotide Res 8:145–266
Perry SV, Cole HA, Frearson N, Moir AJG, Nairn AC, Solaro RJ (1978) Phosphorylation of the myofibrillar proteins. Proc 12 th FEBS Meeting 54:147–159
Purchio AF, Erikson E, Collett MS, Erikson RL (1981) Comparison of the Rous sarcoma virus transforming gene product, pp 60src, and its homologue, pp 60sarc, from normal cells. Cold Spring Harbor Symp 44:in press
Roberts WK, Hovanessian A, Brown RE, Clemens MJ, Keer IM (1976) Interferon-medi-ated protein kinase and low-molecular-weight inhibitor of protein synthesis. Nature 264:477–480
Rubin CS, Rosen OM (1975) Protein phosphorylation. Annu Rev Biochem 44:831–887
Schulman H, Greengard P (1978 a) Stimulation of brain membrane protein phosphorylation by calcium and an endogenous heat-stable protein. Nature 271:478–479
Schulman H, Greengard P (1978 b) Ca2+-dependent protein phosphorylation system in membranes from various tissues, and its activation by “calcium-dependent regulator.” Proc Natl Acad Sci USA 75:5432–5436
Walsh DA, Perkins JP, Krebs EG (1968) An adenosine 3′,5′-monophosphate dependent protein kinase from rabbit skeletal muscle. J Biol Chem 243:3763–3765
Yagi K, Yazawa M, Kakiuchi W, Ohshima M, Uenishi K (1978) Identification of an activator protein for myosin light chain kinase as the Ca2 +-dependent modulator protein. J Biol Chem 253:1338–1340
Zilberstein A, Federman P, Schulman L, Revel M (1976) Specific phosphorylation in vitro of a protein associated with ribosomes of interferon-treated mouse L cells. FEBS Lett 68:119–124
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Greengard, P. (1982). Protein Phosphorylation: An Overview. 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_10
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DOI: https://doi.org/10.1007/978-3-642-68111-0_10
Publisher Name: Springer, Berlin, Heidelberg
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