Phosphorylation cAMP dependent, biochemical

Saez JC, Naim AC, Czemick A, Spray DC, Hertzberg EL, Greengard P, Bennett MVL Phosphorylation of connexin 32, the hepatocyte gap junction protein, by cAMP-dependent protein kinase, protein kinase C and Ca/calmoduUn-dependent protein kinase II. Eur J Biochem 1990 192 263-273. 

The biochemical mechanisms by which cAMP-dependent phosphorylation leads to enhanced IR-PTH release remain to be determined. It is of interest, however, that isoproterenol activates phosphorylation of proteins of similar molecular weight in the rat parotid gland (22), while glucagon stimulates phosphorylation of a protein of molecular weight 19,000 in calcitonin-secreting cultured cells from a medullary carcinoma of the rat thyroid (22) It is conceivable that in all three tissues, activation of exocytosis results from a cAMP-dependent phosphorylation of a critical cellular substrate. 

Consensus sites for phosphorylation were evident in the neuronal NOS enzyme from the predicted protein sequences derived from cDNA analysis. In vitro biochemical studies indicate that nNOS can be phosphorylated by calcium/calmodulin-dependent protein kinase, cAMP-dependent protein kinase, cGMP-dependent protein kinase, and protein kinase C. Phosphorylation of nNOS by all of these enzymes decreases NOS catalytic activity in vitro (Dawson and Snyder, 1994 Bredt etal., 1992 Dinerman etal., 1994a). Calcineurin, a protein phosphatase, dephosphorylates NOS and subsequently increases its catalytic activity (T. M. Dawson etal., 1993). Multiple levels of constitutive nNOS regulation are thus possible by phosphorylation. 

Cox, D.E. Meinke, M.H. Edstrom, R.D. Mechanism of calmodulin inhibition of cAMP-dependent protein kinase activation of phosphorylation kinase. Arch. Biochem. Biophys., 259, 350-362 (1987)... 

Nakao, M., Mizutani, T Bhakta, A., Ribarac-Stepic, N. Moudgil, V.K. (1992). Phosphorylation of chicken oviduct progesterone receptor by cAMP-dependent protein kinase. Arch. Biochem. Biophys., 298, 340-8. 

B.J. Blanchard, R.D. Raghunandan, H.M. Roder, and V.M. Ingram, Hyperphosphorylation of Human TAU by Brain Kinase PK40erk Beyond Phosphorylation by cAMP-dependent PKA Relation to Alzheimer s Disease. Biochem. Biophys. Res. Common., 200,187-194,1994. 

All of the opioid agonists produce some degree of tolerance and physical dependence. The biochemical mechanisms underlying tolerance and physical dependence are unclear. It is known, however, that intracellular mechanisms of tolerance to opioids include increases in calcium levels in the cells, increased production of cAMP, decreased potassium efflux, alterations in the phosphorylation of intracellular and intranuclear proteins, and the resultant return to normal levels of release of most neurotransmitters and neuromodulators. Tolerance to the analgesic effects of opioids occurs rapidly, especially when large doses of the drugs are used at short intervals. However, tolerance to the respiratory depressant and emetic effects of the opioids occurs more slowly. The miotic and constipative effects of the opioids rarely show tolerance. 

The hereditary absence of phenylalanine hydroxylase, which is found principally in the liver, is the cause of the biochemical defect phenylketonuria (Chapter 25, Section B).430 4308 Especially important in the metabolism of the brain are tyrosine hydroxylase, which converts tyrosine to 3,4-dihydroxyphenylalanine, the rate-limiting step in biosynthesis of the catecholamines (Chapter 25), and tryptophan hydroxylase, which catalyzes formation of 5-hydroxytryptophan, the first step in synthesis of the neurotransmitter 5-hydroxytryptamine (Chapter 25). All three of the pterin-dependent hydroxylases are under complex regulatory control.431 432 For example, tyrosine hydroxylase is acted on by at least four kinases with phosphorylation occurring at several sites.431 433 4338 The kinases are responsive to nerve growth factor and epidermal growth factor,434 cAMP,435 Ca2+ + calmodulin, and Ca2+ + phospholipid (protein kinase C).436 The hydroxylase is inhibited by its endproducts, the catecholamines,435 and its activity is also affected by the availability of tetrahydrobiopterin.436... 

Keichee, C., Gambaryan, G., Schulze, E., Marcus, K., Meyer, H. E., Butt, E. (2004). Phosphorylation of mouse LAS P-1 on threonine 156 by cAMP-andcGMP-dependent protein kinase. Biochem. Biophys. Res. Commun. 324, 308-316. 

Adrenoceptors are proteins embedded in the cell membrane that are coupled through a G-protein to effector mechanisms that translate conformational changes caused by activation of the receptor into a biochemical event within the cell. All of the )3-adrenoceptors are coupled through specific G-proteins (Gg) to the activation of adenylyl cyclase (45). When the receptor is stimulated by an agonist, adenylyl cyclase is activated to catalyze conversion of ATP to cyclic-adenosine monophosphate (cAMP), which diffuses through the cell for at least short distances to modulate biochemical events remote from the synaptic cleft. Modu-lationof biochemical events by cAMP includes a phosphorylation cascade of other proteins. cAMP is rapidly deactivated by hydrolysis of the phosphodiester bond by the enzyme phosphodiesterase. The a,-receptor may use more than one effector system, depending on the location of the receptor however, to date the best understood effector system of the a,-receptor appears to be similar to that of the )3-re-... 

Jensen PE, Gong MC, Somlyo A V, Somlyo AP (1996) Separate upstream and convergent downstream pathways of G-protein and phorbol ester-mediated Ca -sensitization of myosin light chain phosphorylation in smooth muscle. Biochemical J 318 469-475 Jiang H, Colbran JL, Francis SH, Corbin JD (1992) Direct evidence for cross-actiration of cGMP-dependent protein kinase by cAMP in pig coronary arteries. J Biol Chem 267 1015-1019... 

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