Protein kinase CS

Manenti S, Sorokine O, Van Dorsseiaer A and Taniguchi H 1992 Affinity purification and characterization of myristoyiated aianine-rich protein kinase C substrate (MARCKS) from bovine brain J. Biol. Chem. 267 22 310-15... 

The spatial and steric requirements for high affinity binding to protein kinase C (PKC), a macromolecule that has not yet been crystallized, were determined. Protein kinase C plays a critical role in cellular signal transduction and is in part responsible for cell differentiation. PKC was identified as the macromolecular target for the potent tumor-promoting phorbol esters (25). The natural agonists for PKC are diacylglycerols (DAG) (26). The arrows denote possible sites of interaction. 

Excitation of smooth muscle via alpha-1 receptors (eg, in the utems, vascular smooth muscle) is accompanied by an increase in intraceUular-free calcium, possibly by stimulation of phosphoUpase C which accelerates the breakdown of polyphosphoinositides to form the second messengers inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 releases intracellular calcium, and DAG, by activation of protein kinase C, may also contribute to signal transduction. In addition, it is also thought that alpha-1 adrenergic receptors may be coupled to another second messenger, a pertussis toxin-sensitive G-protein that mediates the translocation of extracellular calcium. 

S Wang, DW Zaharevitz, R Sharma, VE Marquez, NE Lewm, L Du, PM Blumberg, GWA Milne. The discovery of novel, stnicturally diverse protein kinase C agonists through computer 3D-database pharmacophore search. I Med Chem 37 4479-4489, 1994. 

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

Effect of alteration of heterocyclic nucleus of indolactam V on its isoform selectivity for protein kinase C 95F425. 

Structural basis of protein kinase C activation by heterocyclic tumor promoters 98ACR163. 

The tjipanazoles (18, 19a-d, 20a-b) a group of A-glycosides of indolo-[2,3-a]carbazole, have been isolated from the moderately antifungal extract of the blue-green alga Tolypothrix tjipanasensis. These alkaloids do not exhibit antitumor or protein kinase C (PKC) inhibitory activity, which is in contrast with the... 

Batcho indole synthesis is a useful tool for synthesis of naniral products. As oudined in Scheme 10.6, the Batcho indole synthesis is used for total synthesis of the slime mold alkaloid arcyriacyanin. Such indolocarbazole alkaloids represent a growing number of naniral products isolated from soil organism, slime molds, and marine sources. They are important as andnimor compounds and protein kinase C and topoisomerase inhibitors. 

FIGURE 2.7 Production of second messengers inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG) through activation of the enzyme phospholipase C. This enzyme is activated by the a- subunit of Gq-protein and also by Py subunits of Gj-protein. IP3 stimulates the release of Ca2+ from intracellular stores while DAG is a potent activator of protein kinase C. 

Apelin receptors activate several signalling pathways including coupling through inhibitory G-proteins (G ) and Ras-independent activation of extracellular-regulated kinases (ERKs) via protein kinase C (PKC). The apelin receptor is one of number of G-protein-coupled receptors that can act as an alternative coreceptor for entry into cells of HIV and simian immunodeficiency vims (SIV) strains in human U87 cells expressing CD4 in vitro. Apelin peptides blocks entry of HIV but display different potencies, with apelin-36 being more effective than shorter sequences [3]. 

AChE-R (in purple) Naturally rare, stress-induced variant, which lacks a hydrophobic domain and is incapable of binding to ColQ or PRiMA. Therefore, it remains soluble, and its secreted form shows greater mobility than AChE-S. AChE-R can intra-cellularly interact through its C-terminal tail with the Protein Kinase C Receptor RACK1, a scaffold protein which modifies multiple cellular processes. 

Diacylglycerol is glycerol esterified to two fatty acids at the sn-1 and sn-2 positions. It is a membrane-embedded product of phospholipase C action and an activator of protein kinase C. It is also an intermediate in the biosynthesis of triacylglycerol, phosphatidyletha-nolamine and phosphatidylcholine. 

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. 

Fat Increased glucose transport GLUT4-translocation PI 3-kinase/Akt mediated translocation of GLUT4 into the plasma membrane. Potential involvement of atypical forms of protein kinase C (PKC and A)... 

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