CGMP-regulated kinase

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)... 

The molecular structure of the K a channel in smooth muscle is not known, although based on functional similarities, it would be expected to be a member of the mSlo family. K g channels seem to integrate many vasoactive signals that activate many important signal transduction pathways. The relative importance and regulation of Kca channels through cGMP-protein kinase, cAMP-protein kinase, or direct G-pro-tein activation pathways will be the subject of future research. 

Amoeba GPCR G-protein activation, PIP3 regulation of rho family G proteins, cGMP regulation of myosin kinases, ERK activation 5... 

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 major relaxing transmitters are those that elevate the cAMP or cGMP concentration (Fig. 3). Adenosine stimulates the activity of cAMP kinase. The next step is not clear, but evidence has been accumulated that cAMP kinase decreases the calcium sensitivity of the contractile machinery. In vitro, cAMP kinase phosphorylated MLCK and decreased thereby the affinity of MLCK for calcium-calmodulin. However, this regulation does not occur in intact smooth muscle. Possible other substrate candidates for cAMP kinase are the heat stable protein HSP 20, (A heat stable protein of 20 kDa that is phosphorylated by cGMP kinase. It has been postulated that phospho-HSP 20 interferes with the interaction between actin and myosin allowing thereby smooth muscle relaxation without dephosphorylation of the rMLC.) Rho A and MLCP that are phosphorylated also by cGMP kinase I (Fig. 3). 

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

Protein kinases, in cooperation with other proteins, form multiprotein complexes which are susceptible to activation upon external agonist stimuli. According to different functions in cell-cycle regulation, the conformational changes are initiated by autophosphorylation and dimerization transmitted by the previously discussed second messengers cAMP, cGMP, IP3, PIP3, AA and DAG. 

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