Kinases 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... 

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. 

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. 

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. 

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. 

Studies similar to the substrate specificity studies outlined for oAMP-dependent protein kinase have already begun for other protein kinases such as cGMP-dependent protein kinase ( ), phos-jAiorylase kinase (69-71) and two tyrosine-specific protein kinases (72-75). 

Regulation of activity of cGMP-dependent protein kinases... 

The cGMP-dependent protein kinases have structural elements similar to those of protein kinase A (review Franci and Corbin, 1994 ), and their activity is also regulated by an inhibitory structural element. In contrast to protein kinase A, the regulatory and catalytic functions are localized on one protein chain in cGMP-dependent protein kinases. 

Tlie functions of the cGMP-dependent protein kinases are not as well defined as those of protein kinase A. An important function of cGMP and the cGMP-dependent protein kinases is the regulation of the cytosohc Ca " level. In smooth muscle cells, cGMP brings about a reduction in the Ca, by a mechanism that has not yet been elucidated. 

Stimulation of NO synthase leads to activation of a NO-sensitive guanylyl cyclase. The associated increase in the cGMP level has multiple consequences. The cGMP can stimulate cGMP-dependent protein kinases it can also open cGMP-controUed ion channels. As a consequence, an increase in the intracellular Ca concentration takes place and a Ca signal is produced. NO can influence both protein phosphorylation and InsPs/diacylglycerol and Ca metabolism by this mechanism and activate a broad palette of biochemical reactions in the cell. 

Lohmann, S.M., Vaandrager, A.B., Smolensk , A., Walter, U. and De Jonge, H.R. Distinct and specific functions of cGMP-dependent protein kinases (1997) Trends Biochem Sd. 22, 307-12... 

Furthermore, the LPS signal transduction involves the activation of G proteins, of phospholipases C and D, the formation of diacyl-glycerol (DG) and inositol triphosphate (IP3). DG mediates the stimulation of protein kinase C (PKC) and IP3 induces an increase of cytosolic Ca++ The LPS signaling pathway also involves tyrosine kinases, constitutive nitric oxide (NO) synthase (cNOS), cGMP-dependent protein kinase, Ca channels, calmodulin and calmodulin kinase [27,28], as well as the MAP kinases [29] ERK1, ERK2 and p38 [23], The intracellular events in response to LPS are due to lipid A because they are inhibited by polymyxin B which is known to bind lipid A [27] and they are reproduced by lipids A [30,31]. 

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