Proteine kinase C activity

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

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

The differences between palytoxin and PDBu with respect to kinetics, temperature dependence, and effect on low affinity binding suggest that these two different types of tumor promoters may be acting through different mechanisms. Further, in contrast to PDBu, the effect of palytoxin is not readily reversible (33). To determine where the two pathways differ, we compared the relative ability of palytoxin and PDBu to inhibit EGF binding in protein kinase C depleted cells. Swiss 3T3 cells were depleted of protein kinase C to different extents by exposing confluent quiescent cells to 0, 20, 200, or 2000 nM PDBu for 72 hr. Previous results indicate that this treatment depletes cells of protein kinase C activity in a dose-dependent manner (31). 

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. 

Evidence of a Role for Protein Kinase C Activation in T-Lymphocyte Migration... 

R18. Russell, D. H New aspects of prolactin and immunity A lymphocyte-derived prolactin-like product and nuclear protein kinase C activation. Trends Pharmacol. Sci. 10,40-44 (1989). 

Chen HH, Ma T, Hume AS, et al. 1998. Developmental lead exposure alters the distribution of protein kinase C activity in the rat hippocampus. Biomed Environ Sci 11 61-69. 

Fujimori, K, et at (2005). Protein kinase C activates human lipocalin-type... 

Wang, H. Y. and Friedman, E. Enhanced protein kinase C activity and translocation in bipolar affective disorder brains. Biol. Psych. 40 568-575,1996. 

Friedman, E., Hoau Yan, W., Levinson, D. et al. Altered platelet protein kinase C activity in bipolar affective disorder, manic episode. Biol Psych. 33 520-525,1993. 

Abnormal protein kinase C activity and signaling pathways. 

Moser GJ, Smart RC. 1989. Hepatic tumor-promoting chlorinated hydrocarbon stimulate protein kinase C activity. Carcinogenesis 10(5) 851-856. 

Rotenberg SA, Weinstein IB. 1991. Two polychlorinated hydrocarbons cause phospholipid-dependent protein kinase C activation in vitro in the absence of calcium. Molecular Carcinogenesis 4 477-481. 

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. 

In addition to the importance of Ca2+, PLA2 activity is also regulated by lipocortin (also termed lipomodulin), which is a 40-kDa protein. The inhibitory effect of lipocortin is regulated by its phosphorylation status, acting as an inhibitor of the enzyme when in the dephosphorylated state. Upon cell activation (e.g. by fMet-Leu-Phe), the lipocortin becomes phosphorylated, and PLA2 activity (usually detected as the release of arachidonic acid) increases. Protein kinase C can cause this phosphorylation, and so activation of this kinase may lead to the relief of PLA2 inhibition via phosphorylation of lipocortin. Thus, elevations in the levels of intracellular Ca2+ and production of DAG (required for protein kinase C activation) may co-ordinately activate PLA2. 

E. J. Smart, D. C. Foster, Y. S. Ying, B. A. Kamen, and R. G. Anderson. Protein kinase C activators inhibit receptor-mediated potocytosis by preventing internalization of caveolae. J. Cell Biol. 124 307-313 (1994). 

Mansat, V., Laurent, G., Levada, T., Bettaieb, A., and Jaffrezou, J-P., 1997, The protein kinase C activators phorbol esters and phosphatidylserine inhibit neutral sphingomyehnase activation, ceramide generation and apoptosis triggered by daunorubicin. Cancer Res. 57 ... 

UberaU, F., Oberhuber, H., Maly, K., Zaknun, J., Demuth, L., and Grunicke, H.H., 1991, Hexadecyl-phosphochotine inhibits inositol phosphate formation and protein kinase C activity. Cancer Res. 51 807-812... 

Huang, H.W., Goldberg, E.M. andZidovetzM, R., 1999, Ceramides modulate protein kinase C activity and perturb the stmcture of Phosphatidylchohne/Phosphatidylserine talayers. Biophys. J. 77 1489-1497... 

PMA inhibitor Protein kinase C activator stimulation of caveolae uptake Should be an selective 48,68 ... 

Phorbol esters are described as being protein kinase C activators and should be selective inhibitors for caveolae uptake [1 pM Phorbol 12-myristate 13-acetate (PMA) for 30 minutes] (48,68). The inhibition occurs as quickly as five minutes after adding PMA to cell culture medium and is not reversible within five hours (MA104 cells). However, PMA has several other effects on several other pathways. An example of this is that it has been described to stimulate macropinocytosis and transcytosis (see the following). 

The a.1 receptors are excitatory in their action, while the a2 receptors are inhibitory, these activities being related to the different types of second messengers or ion channels to which they are linked. Thus, a2 receptors hyperpolarize presynaptic membranes by opening potassium ion channels, and thereby reduce noradrenaline release. Conversely, stimulation of ai receptors increases intracellular calcium via the phosphatidyl inositol cycle which causes the release of calcium from its intracellular stores protein kinase C activity is increased as a result of the free calcium, which then brings about further changes in the membrane activity. 

Ingenol (124) Tetracyclic diteipene Ingenol 3-angelate (PEP005) (125)/ Ingenol mebutate Oncology Protein kinase C activation Phase II Peplin 730-733... 

Palal, Srinivasan A, Vig PVS, Desaiah D, Modulation ofcahnoduhn and protein kinase C activities by Penicillium mycotoxins, Int JToxicol 18 91—96, 1999. 

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