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

12-o-Tetradecanoylphorbol-13-acetate (TPA) activates calcium-activated, phospholipid-dependent protein kinase (protein kinase C) partially purified in an ion exchange column from pig epidermis. Protein kinase C was activated by TPA in a concentration-dependent manner with simultaneous addition of Ca2+ and phospholipid. Polyprenoic acid derivative (E5166) which is a newly synthesized retinoic acid derivative, inhibited the TPA activation of protein kinase C. This inhibition may explain the mechanisms by which retinoids inhibit TPA-induced tumor promotion.
Arch Dermatol Res 1986
PMID:Effects of 12-o-tetradecanoylphorbol-13-acetate and polyprenoic acid derivative on calcium-activated phospholipid-dependent protein kinase of pig skin. 381 53

Epidermal cells contain 4 separate surface receptors which are linked to adenylate cyclase. Activation of any one of these receptors leads to the accumulation of cAMP within the cell which in turn leads to the activation of cAMP-dependent protein kinase. The levels of cAMP accumulation within the cell caused by the 4 activators are not the same. Epinephrine, histamine, adenosine, and prostaglandins of the "E" series cause easily measurable concentrations of cAMP within 5 min of exposure. Prostaglandin F2 alpha causes only a small nonsignificant increase. Similarly, 2 phosphodiesterase inhibitors, which inhibit the breakdown of cAMP formed within the cell, differ in their ability to accumulate cAMP when cells are exposed to these agents alone. Isobutylmethylxanthine causes a measurable increase in cAMP, while theophylline, a weak inhibitor of phosphodiesterase, gives a nonsignificant increase in cAMP. Recently, experiments have shown that agents that give only slight increases in cAMP by biochemical measurements, that is, prostaglandins F2 alpha and theophylline, are equally able to activate protein kinase within the cell. Since activation of protein kinase is the only mechanism for an increase in cAMP to have a physiologic effect, all of these agents that do activate protein kinase should cause physiologic effects. Using an explant culture system, we show in this paper that this supposition is correct and that all agents that activate protein kinase do result in inhibition of mitotic activity regardless of whether or not they are able to raise cAMP to a level that can be biochemically measured as being significantly different from the baseline value.
J Invest Dermatol 1983 Dec
PMID:Agents that activate cyclic AMP-dependent protein kinase inhibit explant culture growth and mitotic activity. 619 22

We investigated calcium-activated, phospholipid-dependent protein kinase in pig epidermis. Pig epidermal homogenates were centrifuged at 30,000 g for 30 min, and the supernatant was applied on a DEAE-cellulose column for purification. The partially purified enzyme was stimulated by simultaneous addition of Ca2+ and phospholipid. Successive addition of small amounts of diolein further activated the enzyme activity. The calcium-activated phospholipid-dependent protein kinase preferentially phosphorylated serine residues and its endogenous substrate protein in the pig epidermis has a molecular weight of about 97,000.
J Invest Dermatol 1984 Oct
PMID:Calcium-activated, phospholipid-dependent protein kinase in pig epidermis. 623 57

Pig epidermal slices were incubated with various compounds which increased epidermal cAMP (adenosine 3',5'-monophosphate), and the change in cAMP-dependent protein kinase activity ratio was studied by the method of Cherrington et al (J Biol Chem 251:5209-5218, 1976) with modification. Epinephrine (5 x 10(-5) M), histamine (10(-4) M) and adenosine (10(-3) M), potent agonists of epidermal adenyl cyclase, fully activated the protein kinase (PK) during an incubation of 30 to 45 seconds, that was much shorter than that required for maximal cAMP accumulation under the same conditions (5 min). With such a brief stimulus, the epidermal cAMP-PK system did not become refractory and responded to repeated stimuli. Prostaglandin E2 (PGE2) and isobuthylmethylxanthine (IBMX) and ethanol only partially activated the enzyme. Prostaglandin F2 alpha (PGF2 alpha) and theophylline which were much less effective in increasing epidermal cAMP, activated the enzyme to the same extent as PGE2 and IBMX respectively. These results suggest that protein kinase activation takes place in response to a cAMP increase in small locus of the cell. Such an increase in cAMP can be very small or even not measurable when measured as total cAMP in the tissue homogenate. Also, increases above this level may not be physiologic. It is concluded that measurement of cAMP-dependent protein kinase activity ratio is a more direct and more sensitive way to study the effect of compounds which act through cAMP mediated mechanisms.
J Invest Dermatol 1981 Nov
PMID:Activation of cAMP-dependent protein kinase in epidermis by the compounds which increase epidermal cAMP. 627 Feb 13

Incubation in vitro of full-thickness guinea-pig skin with epinephrine or histamine resulted in the formation of adenosine 3', 5'-cyclic monophosphate (cyclic AMP) and increase in the cyclic AMP-dependent protein kinase activity ratio. The effect was dose-dependent between 10(-5) and 10(-3) M concentration of the agents. Histamine antagonists, diphenhydramine (H1) and cimetidine (H2) prevented stimulation by histamine in a dose-dependent manner suggesting the presence of both types of receptors in full-thickness skin. Cyclic AMP accumulation with a concomitant increase in protein kinase activity denotes that phosphoproteins may have an important role in skin biology.
Br J Dermatol 1982 Jul
PMID:Modulation of adenosine 3', 5'-cyclic monophosphate-dependent protein kinase in skin. 628 49

Microassay procedures for cAMP-dependent protein kinase and phosphorylase were developed which detected these activities in less than 25 micrograms of frozen-dried epidermis from a punch biopsy of skin without homogenization. Using these procedures, the activation of cAMP-dependent protein kinase and phosphorylase by beta-adrenergic stimulation in mouse skin was studied in vivo. Cyclic AMP-dependent protein kinase was stimulated by isoproterenol and inhibited by propranolol. Isoproterenol stimulation also activated phosphorylase a in mouse skin. In normal epidermis and uninvolved and involved epidermis from psoriatic patients no significant differences were found in the activities of cAMP-dependent kinase and phosphorylase a. In all experiments we observed that the unstimulated activity ratios of phosphorylase a/total phosphorylase were around 20-30%; these values were much lower than those hitherto reported and show a preponderance of phosphorylase b rather than a. We suggest that in previous reports where phosphorylase a domination was found, phosphorylase b to a activation occurred during homogenization. The data also suggest that in the steady state no obvious defect in basic activities of cAMP-dependent protein kinase and phosphorylase is observed in psoriatic skin.
J Invest Dermatol 1982 Sep
PMID:Measurement of adenosine 3',5'-monophosphate-dependent protein kinase and phosphorylase activities in in vivo conditions. 628 82

The distribution of adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase and its substrate proteins was analyzed using soluble and particulate fractions of pig epidermal homogenates. When histone was used as a substrate for this enzyme reaction, protein kinase activity was distributed almost equally between the soluble and particulate fractions. However, the effect of exogenously added cAMP was confined almost exclusively to the soluble enzyme. Endogenous protein phosphorylation in the absence of exogenous histone was higher in the particulate fraction than in the soluble fraction, but the stimulating effect of cAMP was observed only in the soluble fraction. These results indicate that cAMP-dependent protein kinase is predominantly localized in the soluble fraction and phosphorylates soluble epidermal proteins. The particulate fraction contains protein kinase which is cAMP-independent and phosphorylates particulate-bound proteins as well as histone. Based on these observations, the soluble fraction was incubated with [gamma-32P]-ATP in the presence or absence of cAMP, and phosphorylated protein was analyzed by SDS disc- or slab-gel electrophoresis followed by autoradiography. Among many proteins whose phosphorylation was slightly increased by cAMP, a protein with Mr approximately 45,000 was found which was markedly phosphorylated in the presence of cAMP. Although this protein corresponds to one of the richest proteins in the epidermal soluble fraction, an important physiologic role for this phosphorylation has not been clarified.
J Invest Dermatol 1983 Feb
PMID:Phosphorylation of pig epidermal soluble protein by endogenous cAMP-dependent protein kinase. 629 35

Cyclic AMP-dependent protein kinase isozymes of pig and human skin (epidermis) were separated by DEAE-cellulose column chromatography after micromodification for small biopsy samples. Clear-cut separations of type I and type II isozymes, which were of about equal amounts, could be obtained only when the ischemia effect was avoided by in vivo freezing of skin and homogenization for less than 10 s. Intradermal injections of epinephrine caused dose-dependent activation of type I isozyme, but not of type II. Injections of other skin adenylate cyclase stimulators such as histamine, adenosine, and prostaglandin E2 elevated the local cyclic AMP levels to not more than 5 pmol/mg protein and also stimulated only the type I isozyme. Incubation of keratome-sliced pig skin under various conditions caused both activation by dissociation and inactivation by reassociation of the subunits, which appeared to be dependent on the cyclic AMP content. Epinephrine added to the incubation medium led to complete activation of both type I and type II isozymes (the intraepidermal cyclic AMP contents ranged from 20-50 pmol/mg protein). The isozymes of normal skin and involved skin of psoriatics showed identical peaks of type I and type II isozymes of equal amounts. The data indicate that protein kinase in the involved skin is not in an activated (by cyclic AMP) state.
J Invest Dermatol 1983 Feb
PMID:Cyclic AMP-dependent protein kinase isozymes of pig skin and human skin from normal and psoriatic subjects. 629 36

Although receptor-specific refractoriness has been suggested to be one of the regulatory mechanisms of epidermal adenylate cyclase systems, its physiologic significance has been a subject of controversy because of the requirement of unusually high concentrations of agonists to induce refractoriness. In order to determine whether the epidermal adenylate cyclase system is regulated through a refractoriness mechanism by suboptimal concentrations of receptor agonists, this study was undertaken using pig skin epidermal adenylate cyclase systems. Pretreatment of pig skin with 0.1-1 microM epinephrine in vitro resulted in the reduction of the maximal epinephrine response (epinephrine-induced cyclic AMP accumulations) to various degrees without alterations in either low or high Km cyclic AMP phosphodiesterase activities. Repeated pretreatments were shown to be more effective in inducing refractoriness than a single pretreatment. Apparently there was no change in the Km value for epinephrine, suggesting that the decrease in epinephrine response represents a reduction in the number but not in the affinity of functional beta-adrenergic adenylate cyclase receptor sites. This refractoriness by low concentrations of catecholamine pretreatment was specific to the beta-adrenergic system, since there was no reduction in histamine response after the epinephrine pretreatment. These results indicate that the epidermal beta-adrenergic adenylate cyclase system is regulated by much lower concentrations of catecholamine than were previously described. It was suggested that physiologic fluctuations of plasma catecholamine levels might have a profound effect on epidermal beta-adrenergic adenylate cyclase responsiveness, resulting in the alteration of the minimal catecholamine level required for the successive activation of cyclic AMP-dependent protein kinase, which is the predominant target of cyclic AMP in epidermis.
J Invest Dermatol 1983 Dec
PMID:Regulation of beta-adrenergic adenylate cyclase responsiveness of pig skin epidermis by suboptimal concentrations of epinephrine. 631 30

Polyamine-dependent protein kinase in cytosol of pig epidermal cells was extracted. The fraction containing this enzyme exhibited multiple polypeptide bands on polyacrylamide gel electrophoresis, including 4 major polypeptide bands and several minor polypeptide bands. A 80 kilodalton (KD) polypeptide, one of the minor polypeptide bands, was phosphorylated by polyamine-dependent protein kinase. Authentic ornithine decarboxylase (ODC) exogenously added was separated into 2 subunits (80 KD and 40 KD) on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and a 80 KD polypeptide was also phosphorylated by polyamine-dependent protein kinase. A 80 KD polypeptide of ODC comigrated with the polypeptide of cytosol which was phosphorylated by polyamine-dependent protein kinase. Kinetic study revealed that the ODC activity decreased as ODC was phosphorylated. Therefore, ODC activity was inhibited by epidermal polyamine-dependent protein kinase-mediated phosphorylation. The overall results indicate that the rapid turnover of ODC might be regulated by a phosphorylation-dephosphorylation reaction without new protein synthesis.
J Invest Dermatol 1984 Oct
PMID:Ornithine decarboxylase activity is inhibited by epidermal polyamine-dependent protein kinase-mediated phosphorylation. 648 Nov 78


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