And protein kinase C

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. 

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. 

Pindur U., Lemster T. Recent Advances in the Synthesis of Carbazoles and Anellated Indoles With Antitumor Activity DNA-Binding Ligands and Protein Kinase C Inhibitors Recent Res. Dev. Org. Bioorg. Chem. 1997 1 33-54 Keywords Diels-Alder reactions of a 4,7-dioxo-indole with carbodienophiles... 

Recent evidence indicates that the 5-HT transporter is subject to post-translational regulatory changes in much the same way as neurotransmitter receptors (Blakeley et al. 1998). Protein kinase A and protein kinase C (PKC), at least, are known to be involved in this process. Phosphorylation of the transporter by PKC reduces the Fmax for 5-HT uptake and leads to sequestration of the transporter into the cell, suggesting that this enzyme has a key role in its intracellular trafficking. Since this phosphorylation is reduced when substrates that are themselves transported across the membrane bind to the transporter (e.g. 5-HT and fi -amphetamine), it seems that the transport of 5-HT is itself linked with the phosphorylation process. Possibly, this process serves as a homeostatic mechanism which ensures that the supply of functional transporters matches the demand for transmitter uptake. By contrast, ligands that are not transported (e.g. cocaine and the selective serotonin reuptake inhibitors (SSRIs)) prevent the inhibition of phosphorylation by transported ligands. Thus, such inhibitors would reduce 5-HT uptake both by their direct inhibition of the transporter and by disinhibition of its phosphorylation (Ramamoorthy and Blakely 1999). 

Relationship between flavonoid structure and inhibition of phos-phatidylinositol 3-kinase a comparison with tyrosine kinase and protein kinase C inhibition Biochemical Pharmacology 53, 1649-57. 

Sakamoto, W., Fujie, K., Handa, H., Ogihara, T. and Mino, M. (1990). In vivo inhibition of superoxide production and protein kinase C activity in macrophages from vitamin E-treated rats. Intemat. J. Vit. Nutr. Res. 60, 338-342. 

The PLCy and Protein Kinase C Signal-Transduction Pathway.251... 

Developmental exposure to Pb or Mm affect signal transduction process, possibly related to the modulation of nitric oxide as well as alterations in receptor-mediated phosphoinositide hydrolysis and protein kinase C (rats)... 

Uramura K., Funahashi H., Muroya S. et at (2001). Orexin-a activates phospholipase C- and protein kinase C-mediated Ca2+ signaling in dopamine neurons of the ventral tegmental area. NeuroReport 12, 1885-9. 

Mestek A, Hurley JH, Bye LS et al. The human k opioid receptor modulation of functional desensitization by calcium/cal-modulin-dependent protein kinase and protein kinase C. J Neurosci 1995 15 2396-2406. 

Chen Y, Yu L. Differential regulation by cAM P-dependent protein kinase and protein kinase C of the k opioid receptor coupling to a G protein-activated K+ channel. J Biol Chem 1994 269 7839-7842. 

Cox, D. A. and Cohen, M. L. 5-HT2B receptor signaling in the rat stomach fundus dependence on calcium influx, calcium release and protein kinase C. Behav. Brain Res. 73 289-292,1996. 

Fiebich, B. L., Schleicher, S., Spleiss, O., Czygan, M. and Hull, M. Mechanisms of prostaglandin E2-induced interleukin-6 release in astrocytes possible involvement of EP4-like receptors, p38 mitogen-activated protein kinase and protein kinase C. /. Neurochem. 5 950-958,2001. 

Reduces intracellular inositol and protein kinase C isozymes ... 

Chen TC,SuS, FryD,Liebes L (2003) Combination therapy with irinotecan and protein kinase C inhibitors in malignant glioma. Cancer 97 2363-2373... 

Takami M, Takahashi N, Udagawa N, Miyaura C, Suda K, Woo JT, Martin TJ, Nagai K, Suda T (2000) Intracellular calcium and protein kinase C mediate expression of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin in osteoblasts. Endocrinology 141 4711 -4719... 

Zamponi GW, Bourinet E, Nelson D, Nargeot J, Snutch TP (1997) Crosstalk between G proteins and protein kinase C mediated by the calcium channel alphal subunit. Nature 385 442 146... 

It is known that protein kinase C can phosphorylate a number of key oxidase components, such as the two cytochrome b subunits and the 47-kDa cytoplasmic factor. This process is prevented by protein kinase C inhibitors such as staurosporine (although it is now recognised that this inhibitor is not specific for protein kinase C), which also inhibits the respiratory burst activated by agonists such as PMA. However, when cells are stimulated by fMet-Leu-Phe, translocation of pAl-phox to the plasma membrane can occur even if protein kinase C activity is blocked - that is, phosphorylation is not essential for the translocation of this component in response to stimulation by this agonist. Similarly, the kinetics of phosphorylation of the cytochrome subunits do not follow the kinetics of oxidase activation, and protein kinase C inhibitors have no effect on oxidase activity elicited by some agonists -for example, on the initiation of the respiratory burst elicited by agonists such as fMet-Leu-Phe (Fig. 6.14). Furthermore, the kinetics of DAG accumulation do not always follow those of oxidase activity. Hence, whilst protein kinase C is undoubtedly involved in oxidase activation by some agonists, oxidase function is not totally dependent upon the activity of this kinase. 

Hrdina P, Faludi G, Li Q, Bendotti C, Tekes K, Sotonyi P, Palkovits M. (1998). Growth-associated protein (GAP-43), its mRNA, and protein kinase C (PKC) isoenzymes in brain regions of depressed suicides. Mol Psychiatry. 3(5) 411-8. 

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