Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Skin from hairless mice was incubated with two synthetic retinoids, isotretinoin and etretinate, and the cAMP content as well as the activity of cAMP-dependent protein kinase were determined. A crude plasma membrane preparation was used to measure adenylyl cyclase activity. Neither isotretinoin (10(-6) and 10(-5)M) nor etretinate (10(-6)-10(-4)M) produced any significant changes in adenylyl cyclase activity. Tissue cAMP levels also remained unaltered after treatment with these retinoids. Although the protein kinase activity ratios remained constant over the concentration range of each retinoid, absolute protein kinase activity was stimulated by treatment with etretinate. These data suggest that cAMP may not mediate the action of retinoids in skin, and that the stimulation of protein kinase activity caused by etretinate probably involves an alternative mechanism.
Arch Dermatol Res 1985
PMID:Cyclic AMP and cyclic AMP-dependent protein kinase in mouse skin. II. In vitro effects of isotretinoin and etretinate. 300 9

Phospholipid-sensitive, Ca++-dependent protein kinase activity was investigated in the cytosol of melanoma cells. A protein kinase system was partially purified, and enzyme activity was found to be modulated by palmitoyl-carnitine. In order to link the actions of palmitoyl-carnitine on phospholipid-sensitive protein kinase activity and the already reported role of protein kinase C in cell division, we studied the action of palmitoyl-carnitine on melanoma cell growth by measuring colony forming ability in a soft agar culture system. Palmitoyl-carnitine was found to inhibit cell growth in a dose-dependent manner. These findings suggest that palmitoyl-carnitine (or long-chain acylcarnitine), a naturally occurring metabolite, may play a key role in the onset of cell division. We suggest that the action of palmitoyl-carnitine on phospholipid-dependent protein kinase activity is in part related to the molecular events linking protein kinase C activity and the ionic events in the initiation of cell growth.
Br J Dermatol 1988 Aug
PMID:Modulation by palmitoyl-carnitine of calcium activated, phospholipid-dependent protein kinase activity and inhibition of melanoma cell growth. 316 38

Tumor promoting phorbol esters, such as 12-0-tetradecanoylphorbol-13-acetate (TPA), when applied topically to mouse skin cause inflammation and hyperplasia. The major cellular phorbol ester receptor is a calcium and phospholipid dependent protein kinase, protein kinase C (PK-C). PK-C is directly activated by TPA and most of the responses of cells to TPA appear to be mediated by PK-C. This suggests that PK-C may play a key role as a mediator of inflammation and growth in TPA treated mouse skin. Sphingosine has been reported to be a potent inhibitor of PK-C in vitro and in intact leukocytes. We therefore have investigated the effects of sphingosine upon TPA-induced inflammation, hyperplasia, induction of ornithine decarboxylase (ODC) activity and ODC mRNA, and activation of PK-C in mouse skin. The results demonstrate that sphingosine is a potent inhibitor of all of the TPA-induced responses examined. These data are compatible with the hypothesis that PK-C is a major mediator of the phorbol ester response in mouse skin. Furthermore, PK-C inhibitors may have therapeutic potential in inflammatory skin diseases such as psoriasis.
J Invest Dermatol 1988 Nov
PMID:Sphingosine inhibits phorbol ester-induced inflammation, ornithine decarboxylase activity, and activation of protein kinase C in mouse skin. 317 Dec 22

The activity of phospholipid/Ca2+-dependent protein kinase (PKc) was measured in the membrane and cytosolic fractions of normal and psoriatic human fibroblasts. The psoriatic fibroblasts displayed higher membrane-associated PKc activity than normal cells. In contrast, no significant difference in PKc activities was observed in cytosolic fractions from normal and psoriatic fibroblasts. These data suggest that PKc is preferentially associated with the membrane in psoriatic fibroblasts and that such elevated PKc activity in membranes may play a role in the pathogenesis of this disease.
J Invest Dermatol 1988 Mar
PMID:Increased protein kinase C activity in fibroblast membranes from psoriatic patients. 334 60

Previous studies have demonstrated elevated cyclic-AMP-specific phosphodiesterase (PDE) activity in mononuclear leukocytes (MNL) from patients with atopic dermatitis (AD). We questioned whether increased kinase activation could account for this observation. In these studies, we measured abnormally lower basal calcium/phospholipid-dependent protein kinase (PK-C) phosphorylation in MNL from patients with AD. Basal cAMP-dependent protein kinase (PK-A) phosphorylation was concomitantly higher in MNL from patients with AD. These results are in agreement with earlier reports that PK-A activity may have a negative influence on PK-C activity in certain cell systems. Stimulation with the H1-histamine agonist, thiazolylethylamine (TEA), of MNL from normal donors but not patients with AD, resulted in statistically significant increases in PK-C phosphorylation. This implies receptor down regulation or functional desensitization in AD cells. Altered basal protein kinase phosphorylation and abnormal response to selective histamine agonists seen in MNL from patients with AD could explain elevated PDE activity.
J Invest Dermatol 1988 Apr
PMID:Altered leukocyte protein kinase activity in atopic dermatitis. 335 35

Tumor-promoting phorbol esters such as 12-0-tetradecanoylphorbol-13-acetate (TPA) cause epidermal inflammation and hyperplasia similar to that observed in psoriasis. Recent evidence suggests that these effects are mediated by a calcium/phospholipid-dependent protein kinase (protein kinase C), which is quantitatively the major cellular phorbol ester receptor. This report describes the partial purification and biochemical properties of this enzyme from adult human epidermis. Protein kinase C activity was purified 30-fold from high speed supernatants prepared from homogenates of keratome biopsies obtained from healthy volunteers. The partially purified preparation had a specific activity of 1.2 nmol/min/mg protein and an apparent molecular weight of 79,400. Activity was dependent on the presence of calcium and phosphatidylserine. At low calcium concentration (less than 0.1 mM) activity was greatly stimulated by 1,2-dioleoylglycerol. TPA mimicked the effect of diglyceride on enzyme activity, and the partially purified enzyme specifically bound phorbol dibutyrate (Kd = 2 nM). Protein kinase C activity was also present in the membrane fraction from adult human epidermis, and possessed properties similar to those of the cytosolic enzyme. We conclude that protein kinase C is present in human epidermis and is activated by TPA in a manner similar to that described for this enzyme from other tissues. These data lay the foundation for studying the role of protein kinase C in the regulation of epidermal growth and maturation.
J Invest Dermatol 1987 Nov
PMID:Purification and characterization of calcium/phospholipid-dependent kinase from adult human epidermis. 347 19

Endogenous calcium-activated, phospholipid-dependent protein kinase phosphorylates pig epidermal protein. Pig epidermis was homogenized and centrifuged at 30,000 X g for 30 min. The supernatant was incubated with or without calcium and phospholipid. A 97 kD soluble protein from pig epidermis was phosphorylated in the presence of calcium and phosphatidylserine. The phosphorylation reaction occurred immediately. With the use of two-dimensional polyacrylamide gel electrophoresis, it was shown that the 97 kD fragment was a basic protein, and that several small proteins were also phosphorylated. The characterization of these proteins is yet to be undertaken.
Arch Dermatol Res 1986
PMID:Phosphorylation of soluble pig epidermal proteins by endogenous calcium-activated, phospholipid-dependent protein kinase. 356 39

We recently showed a deficiency of cyclic AMP (cAMP)-dependent protein kinases in psoriatic cells. In this work the effects of retinoids on cAMP-dependent protein kinases of fibroblasts from 7 normal subjects and 7 psoriatic patients were studied. The levels of RI and RII (two forms of the cAMP-dependent protein kinases) present in control and retinoic acid-treated cells were quantitated by photoaffinity labeling with [8-azido-32P]cAMP. In psoriatic fibroblasts the levels of RII are decreased or undetectable compared with those of normal fibroblasts both in the cytosolic and membrane fractions. The amount of RI was normal in the cytosol of fibroblasts of 5 out of 7 patients and decreased in 2 patients. Membrane-associated levels of RI were decreased in 5 patients and normal in 2 patients. Retinoic acid treatment induces an increase in the amount of RI and RII regulatory subunits when they are deficient in the cytosolic and membrane fractions of psoriatic fibroblasts. Retinoic acid had no effect on RI and RII in normal fibroblasts. In addition, with in vitro retinoic acid treatment the cAMP-dependent protein kinase activity, measured in the fibroblasts of 4 psoriatic patients, was increased in the cytosol in 2 patients and in the membranes in all 4 patients. In these studies, comparable results were obtained with fibroblasts cultured from involved and uninvolved skin. This in vitro effect of retinoids on cAMP-dependent protein kinases in psoriatic fibroblasts may help to explain some of the in vivo therapeutic effects of retinoids.
J Invest Dermatol 1987 Jul
PMID:Retinoid treatment of human psoriatic fibroblasts induces an increase in cyclic AMP-dependent protein kinase activity. 359 99

Calcium, phospholipid-dependent protein kinase (C-kinase) was partially purified from skin of hairless mice. This enzyme activity was stimulated 6- to 15-fold in the presence of calcium and either diolein (DO), phosphatidyl serine (PS), or a mixture of the two. Tumor promoter, phorbol 12-myristate 13-acetate (PMA), also activated the enzyme either in the presence or in the absence of PS. beta-Carotene, retinol, retinal, retinoic acid, etretinate (trimethyl methoxyphenyl analog of retinoic acid), and isotretinoin (13-cis-retinoic acid) were tested for their effects on enzyme activity. Retinoic acid, etretinate, and isotretinoin stimulated enzyme activity in the absence of PS-DO, but inhibited PS-DO stimulated activity. The remaining compounds had no significant effect of C-kinase. In the presence of PS alone, these 3 retinoids had no effect on enzyme activity whereas retinoic acid and isotretinoin exhibited a dual effect of C-kinase in the presence of DO alone. Although the active retinoids seem to compete for binding sites on the enzyme with DO, the overall interaction among retinoids, DO, PS, and PMA appears to be more complex.
J Invest Dermatol 1986 Mar
PMID:Retinoid effect on calcium, phospholipid-dependent protein kinase from mouse skin. 374 56

The biochemical characteristics of cyclic AMP-dependent protein kinase in calf-snout epidermis were investigated. The activity of cyclic AMP-dependent protein kinase was higher in the lower layer than the upper layer of epidermis. The supernatant of homogenates of the lower layer of calf-snout epidermis was fractionated by DEAE-cellulose chromatography and contained two major peaks of protein kinase activity stimulated by cyclic AMP. This chromatographic pattern is similar to that referred to as Type I and Type II of cyclic AMP-dependent protein kinase in bovine muscle. Both peaks of cyclic AMP-dependent protein kinase in calf-snout epidermis could phosphorylate keratin polypeptides in vitro. The phosphorylation reaction was activated by cyclic AMP and inhibited by a heat-stable inhibitor of cyclic AMP-dependent protein kinase. When Type II enzyme of cyclic AMP-dependent protein kinase was incubated with [gamma-32P]ATP in the absence of substrates, such as histone or keratin polypeptides, the 54,000 dalton protein was phosphorylated and this autophosphorylation was inhibited by the addition of 10 microM cyclic AMP. These results suggest that cyclic AMP-dependent protein kinase in calf-snout epidermis has properties similar to those in bovine muscle and plays an important role in the phosphorylation of keratin polypeptides in calf-snout epidermis.
Arch Dermatol Res 1986
PMID:Cyclic AMP-dependent protein kinase in calf-snout epidermis. 375 34


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