Protein kinase-A

Protein kinase A activation usually promotes, whereas protein kinase C activation retards, apoptosi.s. 

I. Ser/Thr protein kinases A. Cyclic nncleotide-dependent cAMP-dependent (PKA) —R(R/K)X(S /T ) — cAMP... 

III. Tyr protein kinases A. Cytosolic tyrosine kinases src, fgr, abl, etc.) B. Receptor tyrosine kinases (RTKs) Plasma membrane receptors for hormones such as epidermal growth factor (EGF) or platelet-derived growth factor (PDGE) Raf (a protein kinase)... 

AKAPs are a diverse family of about 75 scaffolding proteins. They are defined by the presence of a structurally conserved protein kinase A (PKA)-binding domain. AKAPs tether PKA and other signalling proteins to cellular compartments and thereby limit and integrate cellular signalling processes at specific sites. This compartmentalization of signalling by AKAPs contributes to the specificity of a cellular response to a given external stimulus (e.g. a particular hormone or neurotransmitter). 

Tasken K, Aandahl EM (2004) Localized effects of cAMP mediated by distinct routes of protein kinase A. Physiol Rev 84 137-167... 

GRKs, protein kinase A and protein kinase C have been ICI 118,551... 

Heterologous desensitization is a form of desensitization which does not require agonist binding of the receptor. Second messenger dependent kinases such as protein kinase A (PKA) and protein kinase C (PKC) are involved in this form of receptor desensitization. Heterologous desensitization simply depends on the overall kinase activity which is regulated by many different stimuli. 

Protein kinase A (PKA) is a cyclic AMP-dependent protein kinase, a member of a family of protein kinases that are activated by binding of cAMP to their two regulatory subunits, which results in the release of two active catalytic subunits. Targets of PKA include L-type calcium channels (the relevant subunit and site of phosphorylation is still uncertain), phospholam-ban (the regulator of the sarcoplasmic calcium ATPase, SERCA) and key enzymes of glucose and lipid metabolism. 

The antisense oligonucleotide LErafAON against the serine/threonine kinase c-Raf has been tested in phase I clinical trials. The antisense oligonucleotides ISIS-5132, which also inhibits c-Raf, and ISIS-3521, which inhibits PKC, went through different phase clinical trials with solid tumour patients. Unfortunately, no objective responses occurred with these PKI. GEM-231, an oligonucleotide targeting the RIa subunit of protein kinase A is currently undergoing phase I/II clinical trials alone or in combination with traditional therapy for the treatment of solid cancers [3]. 

Sarcoplasmic calcium ATPase this enzyme utilizes the energy gained from hydrolysis of ATP to pump calcium from the cytosol into the stores of the sarcoplasmic reticulum. Its activity is negatively regulated by the closely associated protein phospholamban, and this inhibition is relieved upon phosphorylation of phospholamban by protein kinase A (PKA). 

Protein Folding Problem Protein Kinase Protein Kinase A Protein Kinase C Protein Kinase Inhibitors Protein Phosphatases Protein Sorting... 

MLCK itself is phosphorylated by cyclic-AMP activated protein kinase, (protein kinase A) and cyclic-GMP activated protein kinase, (protein kinase G). Protein kinase A will phosphorylate MLCK at two sites and protein kinase G at one in some cases and two in others. These differences seem to be important in how the individual smooth muscle cells are regulated. 

Figure 6. A hypothetical scheme for the control of the number of active crossbridges in smooth muscle. Following the activation of a smooth muscle by an agonist, the concentrations of intermediates along the main route begins to build up transiently. This is shown by the thickened arrows. Also, cAMP is generated which is universally an inhibitor in smooth muscle. Cyclic AMP in turn combines with protein kinase A, which accounts for most of its action. The downstream mechanisms, however, are not well worked out and at least three possibilities are likely in different circumstances. First, protein kinase A is known to catalyze the phosphorylation of MLCK, once phosphorylated MLCK has a relatively lower affinity for Ca-calmodulin so that for a given concentration of Ca-calmodulin, the activation downstream is reduced. The law of mass action predicts that this inhibition should be reversed at high calcium concentrations. Other cAMP inhibitory mechanisms for which there is evidence include interference with the SR Ca storage system, and activation of a MLC phosphatase.

PKR Double-stranded RNA-activated protein kinase A serine threonine kinase that phos-phorylates eIF2a on serine residue 51 when activated... 

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