Cyclic nucleotide-dependent protein activation

Wagner LE, 2nd, Li WH, Yule DI (2003) Phosphorylation of type-1 inositol 1,4,5-trisphosphate receptors by cyclic nucleotide-dependent protein kinases a mutational analysis of the functionally important sites in the S2+ and S2- splice variants. J Biol Chem 278 45811-7 Wall ME, Francis SH, Corbin JD, Grimes K, Richie-Jannetta R, Kotera J, Macdonald BA, et al. (2003) Mechanisms associated with cGMP binding and activation of cGMP-dependent protein kinase. Proc Natl Acad Sd USA 100 2380-5... 

E. Butt, M. Bernhardt, A. Smolensk , P. Kotsonis, L. G. Frohlich, A. Sickmann, H. E. Meyer, S. M. Lohmann and H. H. Schmidt, Endothelial nitric-oxide synthase (type III) is activated and becomes calcium independent upon phosphorylation by cyclic nucleotide-dependent protein kinases. J Biol Chem 275, 5179-5187 (2000). 

Kuo, J. F., and Greengard, P. (1970). Cyclic nucleotide-dependent protein kinases VI. Isolation and partial purification of a protein kinase activated by guanosine 3, 5 -monophosphate. J. Biol. Chem. 245, 2493-2498. 

The frequency and amplitude of calcium sparks are modulated by SR calcium load, protein kinase C (PKC) and cyclic nucleotides/cyclic nucleotide-dependent protein kinases (Bonev et al. 1997 Porter et al. 1997). Calcium spark frequency decreases following activation of PKC (Bonev et al. 1997). This effect appears to be mediated by a direct action of PKC on... 

Other evidence for the involvement of a G-protein in the action of insulin has come from studies by Walaas and co-workers [104]. They have demonstrated that insulin stimulated the activity of a cyclic AMP-dependent protein kinase activity in sarcolemma membranes. As this effect of insulin was enhanced if micromolar concentrations of GTP-binding protein were present, they suggested that a guanine nucleotide regulatory protein was involved in the hormonal control of this kinase. Indeed, cholera toxin also appeared to obliterate this action of insulin, as it did the effect of insulin on liver adenylate cyclase and the peripheral plasma membrane cyclic AMP phosphodiesterase in liver. 

For the receptors that bind atrial natriuretic peptides and the peptides guanylin and uroguanylin, the intracellular domain is not a protein kinase but rather a guanylyl cyclase that synthesizes the second messenger cyclic guanosine monophosphate (cyclic GMP), which activates a cyclic GMP-dependent protein kinase (PKG) and can modulate the activities of several cyclic nucleotide phosphodiesterases, among other effectors. 

In most cases, cyclic AMP functions by activating the isoforms of cyclic AMP-dependent protein kinase (PKA), and cyclic GMP activates a PKG. Recently, a number of additional actions of cyclic nucleotides have been described, all with pharmacological relevance. 

Inoue, M., Kishimoto, A., Takai, Y., and Nishizuka, Y., 1977, Studies on a cyclic nucleotide-independent protein kinase and its proenzyme in mammalian tissues. II. Proenzyme and its activation by calcium-dependent protease from rat brain, /. Biol. Chem. 252 7610. 

Uzunov, P., Gnegy, M. E., Revuelta, A., and Costa, E., 1976, Regulation of the high Km cyclic nucleotide phosphodiesterase of adrenal medulla by the endogenous calcium-dependent-protein activator, Biochem. Biophys. Res. Commun. 70 132. 

Synthesized by soluble guanylyl cyclase and particulate guanylyl cyclase from guanosine triphosphate (GTP). Nitric oxide activates soluble guanylyl cyclase to enhance cyclic GMP production that contributes to various NO actions. Cyclic GMP is hydrolyzed by phosphodiesterases. Cyclic GMP binds to and activates cGMP-dependent protein kinase, phosphodiesterases, and Cyclic Nucleotide-regulated Cation Channels. 

Cyclic nucleotides are made in response to receptor activation. The receptor activates a G-protein that, in turn, activates adenylyl cyclase to make the cyclic nucleotide. To complete the signaling, the increase in cAMP concentration activates a specific protein kinase (serine/threo-nine), cAMP-dependent protein kinase (A kinase) (Fig. 9-7). To turn off the signaling pathway, the cyclic nucleotides are destroyed by enzymes called phosphodiesterases. These cleave cAMP to AMP. 

ATP -I- T-protein = ADP -I- 0-phospho-T-protein (activated by tubulin. Different from EC 2.7.1.123 Ca /calmodulin-dependent protein kinase not activated by calmodulin, cyclic nucleotides or Ca. Involved in the formation of paired helical filaments in brain. See comment on EC 2.7.1.37 protein kinase)... 

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