Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.11 (AMPK)
 12,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vitamin A inhibits growth and increases the activity of cAMP-dependent protein kinase in B16 mouse melanoma cells. In this report we show that retinoic acid (RA) treatment of intact cells alters their subsequent in vitro protein phosphorylation, but we could not demonstrate any changes in in vivo protein phosphorylation. A 48-h treatment with RA results in a concentration-dependent decrease of protein phosphorylation of a 95K molecular weight (MW) protein in both supernatant and particulate fractions. The phosphorylation of this protein does not appear to be regulated by cAMP. Proteins at 92K and 82K MW in the supernatant fraction are increased in phosphorylation. The former (but not the latter) is regulated by cAMP. In the particulate fraction a variety of proteins 12K-68K MW are increased in phosphorylation, as the cells are treated with increasing amounts of RA. The phosphorylation of most of these proteins is regulated by cAMP. Another inhibitor of B16 cell growth, melanocyte-stimulating hormone (MSH) also alters protein phosphorylation. At short incubation periods (1 h), this hormone stimulates phosphorylation of a number of proteins (17-40K MW), while in longer incubation periods (48 h) phosphorylation is inhibited. All of these phosphorylations appear to be regulated by cAMP. We attempted to repeat these observations using intact-cell phosphorylation with 32PO4. In two experiments we saw small changes in the phosphorylation of proteins. In most experiments, however, we could find no change in the phosphoproteins. Further experiments have led us to question the in vivo phosphorylation, since treatment of the cells with MSH, cholera toxin, or db-cAMP also did not affect intact-cell protein phosphorylation. We have previously documented that under these latter conditions cAMP levels are greatly elevated and cAMP-dependent protein kinase is activated. The in vitro phosphorylation results suggests that in RA-treated cells, kinase activities and/or protein substrate levels are changing. However, the physiological significance of the particular MW phosphoproteins changes we have described must await resolution of the in vivo phosphorylation data.
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PMID:The effect of retinoic acid on protein phosphorylation in mouse melanoma cells. 301 73

Protein kinase C (PKC) is a ubiquitous enzyme linked to transmembrane signal transduction. It regulates agonist-mediated activation of intracellular events that result in growth and differentiation in a variety of cells and tissues. PKC is the cellular receptor for phorbol ester tumor promoters, such as 12-O-tetradecanoylphorbol-13-acetate (TPA), that bind to, and directly activate, this enzyme. Vitamin A analogs (retinoids) have been known to antagonize biologic effects of phorbol esters, e.g., promotion of skin tumor formation; however, the extract mechanism(s) of this action is not clear. To analyze the effects of retinoids on T-cell-derived PKC, we partially purified the enzyme from human leukemic T cells (Jurkat) and examined the effects of different vitamin A analogs on its activity. Furthermore, the regulatory effects of retinoids on PKC activity were compared with those of common membrane phospholipids. Retinal inhibited PKC activation induced by TPA, as well as by diacylglycerol, the physiologic activator of PKC. The observed inhibition resulted from competition with phospholipid (phosphatidylserine) and was selective for the phospholipid-dependent C kinase; cAMP-dependent protein kinase, which is phospholipid-independent, was not affected by retinal. The inhibitory effect of retinal on PKC activity was similar to that of phosphatidylcholine. Retinoic acid, in contrast to retinal, induced a Ca2+-dependent activation of PKC, thus substituting for phosphatidylserine. Furthermore, PKC activation by retinoic acid was similar to that by phosphatidylserine, the natural phospholipid cofactor, in that both could be inhibited by phosphatidylcholine and augmented by phosphatidylinositol. The inhibition or activation of PKC by retinal or retinoic acid, respectively, was independent of whether the terminal aldehyde (retinal) or carboxyl (retinoic acid) groups were in the trans or cis configuration. Other vitamin A analogs tested did not affect PKC activity. The results demonstrate that different retinoids and phospholipids may have positive or negative cooperativity in PKC activation, thereby regulating its enzymatic activity and affecting the resulting intracellular activation events. These findings suggest that at least part of the biologic effects of retinoids in general, and their modulation of T-cell function in particular, may be mediated via the influence of their intracellular metabolites on PKC, and that this mechanism may account for some of the antagonistic effects of retinoids on TPA-mediated responses in cells.
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PMID:Regulation of T-cell-derived protein kinase C activity by vitamin A derivatives. 326 37