Protein kinase, cGMP dependent

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. 

Protein kinase, cGMP dependent bovine lung... 

Three different proteins appear to mediate the cellular actions of cGMP cGMP-dependent protein kinase, cGMP-bin g cAMP phosphodiesterase and cGMP-regulated ion channels (Walter, 1989)... 

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 (cAMP and cGMP) are formed enzymatically from the corresponding triphosphates. As ubiquitous second messengers, they mediate many cellular functions which are initiated by first (extracellular) messengers. Their prime targets in eucaryotic cells are protein kinases ( cyclic AMP-dependent protein kinase, cyclic GMP-dependent protein kinase), ion channels and ensymes. 

Hofmann F, Feil R, Kleppisch T et al (2006) Function of cGMP-dependent protein kinases as revealed by gene deletion. Physiol Rev 86 1-23. 

Cyclic-AMP Response Element Binding Protein Cyclic GMP-dependent Protein Kinase Cyclic GMP-regulated Phosphodiesterases Cyclic Guanosine Monophosphate (Cyclic GMP cGMP)... 

FIGURE 21-6 Schematic illustration of the overall structure and regulatory sites of eleven different phosphodiesterase subtypes. The catalytic domain of the phosphodiesterases are relatively conserved, and the preferred substrate(s) for each type is shown. The regulatory domains are more variable and contain the sites for binding of Ca2+/calmodulin (CaM) and cGMP, as well as GAF and PAS domains. The regulatory domains also contain sites of phosphorylation by cAMP-dependent protein kinase (PKA). 

Wall, M. E., Francis, S. H., Corbin, J. D. et al. Mechanisms associated with cGMP binding and activation of cGMP-dependent protein kinase. Proc. Natl Acad. Sci. U.S.A. 100 2380-2385, 2003. 

Other mechanisms have also been implicated in odor adaptation, including cAMP-dependent phosphorylation of ciliary proteins via protein kinase A G-protein-receptor kinase activity (GRK3), possibly via phosphorylation of the OR Ca2+/calmodulin kinase II (CaMKII) phosphorylation of ACIII cGMP and carbon monoxide [ 31 ]. These latter three mechanisms have been particularly linked to longer-lasting forms of adaptation, on the order of tens of seconds (for CaMKII) or minutes (CO/cGMP). Together with the short-term adaptation described above, these various molecular mechanisms provide the OSN with a number of ways to fine-tune odor responses over time. 

Fig. 4.1. Cellular model illustrating cell types in vascular wall involved in vasorelaxation induced by SERMs. Putative targets of SERMs are indicated within cyan tags. SERMs directly affect L-type VDCC, BK fil subunit in smooth muscle cells, and ER in endothelial cells. L-type VDCC L-type voltage-dependent calcium channel BK calcium-activated large conductance K+ channel PKG protein kinase G eNOS endothelial nitric oxide synthase GC soluble guanylate cyclase cGMP cyclic GM P V electrochemical membrane potential ER estrogen receptor. See text for further details...

Guanylate cyclase signaling pathway also utilizes an enzyme-linked receptor model. The effector enzyme, guanylate cyclase, converts GTP to cGMP, which in turn activates cGMP dependent protein kinase or phosphodiesterases. 

Fig. 9.1 Nitric oxide mediated inhibition of platelet activation. Abbreviations used NO, nitric oxide EDRF, endothelium-derived relaxing factor GC, guanylyl cyclase PDE, phosphodiesterase cGMP-PK, GMP-dependent protein kinase Raplb, small GTPase Raplb ...

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