CGMP-activated protein kinase

Ledoux, S-, Dussaule, J.-C., Chatziantoniou, C-, ArdaiOou, N., Vandermeersch, S., and Ardaillou, R, (1997). Protein kinase A activity modulates natriuretic pepiide-depqndenl cGMP accumulation in renal ceils. Aw. /. Physio . 272, C82-C89. 

Cyclic GMP, at increased levels in the cell, binds to a protein kinase, and activates it. This protein kinase is called cGMP-activated protein kinase. The kinase catalyzes the attachment of a phosphate group to a protein called the IPS receptor. The IPS receptor, in its modified state, then provokes a decline in the level of calcium in the cytoplasm of the muscle cell. The decline in intracellular calcium ions... 

The cGMP-dependent protein kinases are activated by cGMP binding (review Hofmann et al., 2000) and have structural elements similar to those of protein kinase A. In contrast to protein kinase A, the regulatory and catalytic functions are localized on one protein chain in cGMP-dependent protein kinases. Binding of cGMP to the... 

It has also been shown that atrial natriuretic factor (ANP), nitric oxide, and isosorbide dinitrite, which dilate arteries and increase intracellular cGMP levels, activate K tp channels suggesting the possibility that either elevation of cGMP or stimulation of cGMP-dependent protein kinase could activate K jp channels in smooth muscle (e.g., see Murphy and Bray den,... 

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. 

The ANP leceptoi exists in two forms, ANP and ANPg, both of which have been cloned. These membrane-bound guanylate cyclases have a single transmembrane domain, an intracellular protein kinase-like domain, and a catalytic cyclase domain, activation of which results in the accumulation of cychc guanosine monophosphate (cGMP). A third receptor subtype (ANP ) has been identified that does not have intrinsic guanylate cyclase activity and may play a role in the clearance of ANP. 

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. 

The Ca2+-calmodulin complex may also activate nitric oxide synthase (NOS), which binds to a PDZ domain of PSD-95. Activated NOS produces NO from arginine NO, in turn, activates guanylate cyclase, the enzyme that catalyzes the conversion of GTP to the intracellular messenger cGMP, which activates protein kinase G (PKG). 

Among the best studied protein kinases in the brain are those activated by the second messengers cAMP, cGMP, Ca2+ and DAG [4,5]. 

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