Protein kinase C a

Caponigro F, French RC, Kaye SB (1997) Protein kinase C a worthwhile target for anticancer drugs Anticancer Drugs 8(l) 26-33... 

A few enzymes, such as the previously mentioned CNP, are believed to be fairly specific for myelin/oligodendro-cytes. There is much more in the CNS than in peripheral nerve, suggesting some function more specialized to the CNS. In addition, a unique pH 7.2 cholesterol ester hydrolase is also enriched in myelin. On the other hand, there are many enzymes that are not myelin-specific but appear to be intrinsic to myelin and not contaminants. These include cAMP-stimulated kinase, calcium/calmodulin-dependent kinase, protein kinase C, a neutral protease activity and phosphoprotein phosphatases. The protein kinase C and phosphatase activities are presumed to be responsible for the rapid turnover of MBP phosphate groups, and the PLP acylation enzyme activity is also intrinsic to myelin. 

In 2006, Greis and co-workers reported on the application of MALDI-TOF MS as a tool for rapid inhibitor screening [10]. Different kinases (protein kinase C-a, cAMP-dependent protein kinase) in combination with their substrates were assayed, and the inhibitory potencies of staurosporine and three novel compounds were determined. For all four compounds, IC50 values could be determined, and... 

Dean N, McKay R, Miraglia L, Howard R, Cooper S, Giddings ], Nicklin P, Meister L, Ziel R, Geiger T, Muller M, Fabbro D (19 ) Iidiibition of growth of human tumor cell lines in nude mice by an antisense oligonucleotide inhibitor of protein kinase C-a expression. Cancer Res 56 3499-3507 Defranco AL (1991) Immunosuppressants at work. Nature 352 754-755 De las Alas MM, Aebi S, Fink D, Howell SB, Los G (1997) Loss of DNA mismatch repair effects on the rate of mutation to drug resistance. J Natl Cancer Inst 89 1537-1541... 

Newton AC, Johnson JE (1998) Protein kinase C a paradigm for regulation of protein function by two membrane-targeting modules. Biochim Biophys Acta 1376 155-172... 

O Brian CA, Ward NE, Gravitt KR, Gupta KP (1995) The tumor promoter receptor protein kinase C a novel target for chemoprevention and therapy of human colon cancer. Prog Clin Biol Res 391 117-120... 

Dekker, L.V. and Parker, PJ. Protein kinase C a question of specifidty (1994) Trends Biochem. 

AP-1 A major transcriptional activator PKC, PKCa, 3, y Protein kinase C,a, P, y subforms... 

Macica CM, von Hehn CA, Wang LY et al (2003) Modulation of the kv3.1b potassium channel isoform adjusts the fidelity of the firing pattern of auditory neurons. J Neurosci 23 1133 11 Majewski H, Iannazzo L (1998) Protein kinase C a physiological mediator of enhanced transmitter output. Prog Neurobiol 55 463-75... 

Yuen, A.R., J. Halsey, G.A. Fisher, J.T. Holmlund, R.S. Geary,T.J. Kwoh, A. Dorr, and B.I. Sikic. 1999. Phase I study of an antisense oligonucleotide to protein kinase C-a (ISIS 3521/CGP 64128A) in patients with cancer. Clin. Cancer Res. 5 3357-3363. 

Fenn JB, Mann M, Meng CK Electrospray ionization for mass spectrometry of large biomolecules. Science (1989) 246 64-71. Patrick JS, Lagu AL Review applications of capillary electrophoresis to the analysis of biotechnology-derived therapeutic proteins. Electrophoresis (2001) 22 4179-4196. Sowell J, Salon J, Strekowski L, et al Covalent and noncovalent labeling schemes for near-infrared dyes in capillary electrophoresis protein applications. Methods Mol. Biol. (2004) 276 39-75. Moini M Capillary electrophoresis mass spectrometry and its application to the analysis ofbiological mixtures. Anal. Bio-anal. Chem. (2002) 373 466 180. Nemunaitis J, Holmlund JT, Kraynak M, et al. Phase I evaluation of ISIS 3521, an antisense oligodeoxynucleotide to protein kinase C-a, in patients with advanced cancer./. Clin. Oncol. (1999) 17 3586-3595. De Frutos M, Cifuentes A, Diez-Masa JC Differences in capillary electrophoresis profiles of urinary and recombinant erythropoietin. Electrophoresis (2003) 24 678-680. 

E. Zylber-Katz, N.M. Dean, S.D. Rabkin, R.L. Martuza, and R.I. Glazer. 1996.Treatment of glioblastoma U-87 by systemic administration of an antisense protein kinase C-a phosphorothioate oligodeoxy-nucleotide. Mol. Pharmacol. 50 ... 

IP3 and DAG are derived from the membrane lipid phosphatidylinositol 4,5-bisphosphate (which is a phosphorylated derivative of phosphatidylinositol see Topic El) by the action of phospholipase C which is also located in the plasma membrane and, like adenylate cyclase, is activated by G proteins (Fig. 5). One of the main actions of the polar IP3 is to diffuse through the cytosol and interact with Ca2+ channels in the membrane of the ER (Fig. 5), causing the release of stored Ca2+ ions which in turn mediate various cellular responses. The DAG produced by the hydrolysis of phosphatidylinositol 4,5-bisphosphate, along with Ca2+ ions released from the ER, activates protein kinase C, a membrane-bound enzyme that phosphorylates various target proteins, again leading to alterations in a variety of cellular processes (Fig. 5). 

Protein kinase family Rat protein kinase C-a ITBN Cysp 2 CysL 21 HiSa/i 2 CySba... 

Protein kinase C (a, pi, pil, y, 5, s) Calcium, phospholipids diacylglycerols Calphostin C... 

The primary application of LNA has been in antisense therapy due to the aforementioned properties. It has been used to knock down human protein kinase C-a (PKC-ot) with greater efficiency than the corresponding phosphor-othioate ODN, as an inhibitor of human telomerase, to block the synthesis of RNA polymerase II and to inhibit human vascular smooth muscle cell growth. LNA-modified oligonucleotides have also been used in RNA interference (RNAi). ... 

Varnes ME, Chiu SM, Xue EY, Oleinick NL. Photodynamic therapy-induced apoptosis in lymphoma cells translocation of cytochrome c causes inhibition of respiration as well as caspase activation. Biochem Biophys ResCommun 1999 255 673-679. Nowak G. Protein kinase C-a and ERK16 mediate mitochondrial dysfunction, decreases in Active Na-i- transport, and cisplatin-induced apoptosis in renal cells. J Biol Chem 2002 277 43377-43388. 

K. Yoshida, T. Hirata, Y. Akita, Y. Mizukami, K. Yamaguchi, Y. Sorimachi, T. Ishihara and S Kawashia-ma, Translocation of protein kinase C-a, 8 and e isoforms in ischemic rat heart, Biochim. Biophys. Acta 1317, 36-44(1996). 

N. Bowling, X. Huang, G.E. Sandusky, R.L. Fouts, K. Mintze, M. Esterman, P.D. Allen, R Maddi, E. McCall, C.J. Vlahos, Protein kinase C-a and -e modulate connexin-43 phosphorylation in human heart, J Mol Cell Cardiol 33, 789-798 (2001). 

DAG glycerol remains in the plasma membrane. There, it activates protein kinase C, a protein kinase that phosphorylates serine and threonine residues in many target proteins. The specialized DAG-binding domains of... 

An innovative immunochemo-proteomics method was developed that allowed the identification of an inhibitor of the heme-binding protein (83). This method is based on the coupling of a small molecule, bis-indolylmaleimide-III, a known inhibitor of protein kinase C-a, to the FLAG peptidic epitope. This leads to the isolation of binding proteins from a cell lysate via the reaction of the FLAG epitope with anti-FLAG antibody beads. 

Nowak G. Protein kinase C-a and ERK1/2 mediate mitochondrial dysfunction, decreases in Active Na+ transport, and cisplatin-induced apoptosis in renal cells. J Biol Chem 2002 277 43377-43388. 

Liu B, Khan WA, Hannun YA, Timar J, Taylor JD, Lundy S, Butovich I, Honn KV. 12(S)hydroxyeicosatetraenoic acid and 13(S)-hydroxyoctadecadienoic acid regulation of protein kinase C-a in melanoma cells role of receptor-mediated hydrolysis of inositol phospholipids. Proc.Natl.Acad.Sci.U.S.A. 92 (1995) 9323-9327. 

Wang, X.Y., K.R Medzihradszky, D. Maltby, and M.A. Correia (2001). Phosphorylation of native and heme-modified CYP3A4 by protein kinase C A mass spectrometric characterization of the phos-phorylated peptides. Biochemistry 40, 11318-11326. 

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