Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of bradykinin on activation of phosphoinositide turnover, 1,2-diglyceride formation, and growth of cultured adult human keratinocytes were investigated. Keratinocytes specifically bound [3H]bradykinin with high affinity (kd = 3.4 nM) and displayed 1.5 X 10(5) binding sites/cell. Bradykinin caused a rapid dose-dependent increase in inositol trisphosphate (IP3) inositol bisphosphate, and inositol monophosphate. IP3 was maximally increased (fivefold) at 30 s and remained elevated for at least 10 min. Half maximal stimulation of IP3 formation was observed at 27 nM bradykinin. IP3 accumulation was equally elevated by bradykinin and lys-bradykinin but was not stimulated by des-Arg9-bradykinin, indicating that phospholipase C in cultured keratinocytes is coupled to B2 bradykinin receptors. Treatment of keratinocytes with active phorbol ester (TPA) caused a significant inhibition (50%) of bradykinin-induced IP3 accumulation, suggesting negative regulation of phospholipase C by protein kinase C. Bradykinin also caused a significant elevation in 1,2-diacylglycerol (DAG) content. DAG content was maximally elevated (twofold) at 1 min and remained elevated for at least 10 min. Bradykinin also caused a significant (twofold, p less than 0.02) increase in keratinocyte growth. These data demonstrate that bradykinin is a potent agonist of the phospholipase C/protein kinase C signal transduction system in cultured adult human keratinocytes and that activation of this pathway by bradykinin is associated with increased keratinocyte growth.
J Invest Dermatol 1990 Dec
PMID:Bradykinin induces phosphoinositide turnover, 1,2-diglyceride formation, and growth in cultured adult human keratinocytes. 217 49

Protein kinase C, which has an important role in cell surface signal transduction, has at least 7 subspecies. The role of each isozyme remains unknown; however, the distribution of the subspecies has been reported to differ from tissue to tissue. In order to investigate the subspecies of protein kinase C in epidermis, we used monoclonal anti-protein kinase C antibodies against the alpha and beta subspecies and against the gamma subspecies. Protein kinase C activity was detected in both cytosol and membrane bound fractions in the extract of pig epidermis, although with immunohistochemical analysis the enzyme was not detected in the epidermis. The protein kinase C in pig epidermis was extracted and partially purified with DE52 column chromatography and immunoblot analysis was performed. Western blot analysis with each anti-protein kinase C antibody showed protein kinase C of the alpha and/or beta subspecies in pig epidermis. The gamma subspecies of the enzyme was not demonstrated. Since this gamma subspecies has only been demonstrated in the brain, it is regarded not to be present in epidermis. The differing patterns of the expression of the multiple subspecies of protein kinase C may closely related to its specific function in each tissue. The subspecies of the enzyme expressed in the epidermis should be clarified further.
J Dermatol 1990 Jan
PMID:Immunoblot demonstration of protein kinase C in pig epidermis. 232 13

Formation of desmosomal cell-cell contact associated with reorganization of keratin intermediate filaments (KIFs) was observed when cultured cells of a cell line of human skin squamous cell carcinoma were transferred from low (0.07 mM) calcium to high (1.87 mM) calcium medium. At low calcium, cells were dispersed without desmosomal cell-cell contact and the KIFs were mostly concentrated around the nucleus. After 15 min of the transfer, cells contacted each other and formed small colonies and the KIFs initiated to show a radial arrangement. In addition to the cell-cell contact formation and rearrangement of KIFs, the transfer induced fourfold increase of particulate-associated protein kinase C (C-kinase) activity. When 12-O-tetradecanoyl phorbol-13-acetate (PMA), which specifically activates C-kinase, was added to the cells grown at low calcium medium, cell-cell contact formation and radial arrangement of KIF bundles almost identical to those induced by the transfer to high calcium medium were observed. These data suggest a correlation between an increase in C-kinase activity and formation of cell-cell contacts associated with rearrangements of KIFs.
J Invest Dermatol 1989 Feb
PMID:Correlation between cell-cell contact formation and activation of protein kinase C in a human squamous cell carcinoma cell line. 246 49

Exposure of pig epidermal sheets to the protein kinase C (PKC) activator, phorbol 12-myristate, 13-acetate (PMA) resulted in an increase in forskolin-induced cyclic AMP accumulation in the epidermis. Cholera toxin-induced cyclic AMP accumulation was moderately increased by PMA treatment, but this was not statistically significant. On the other hand, receptor-mediated adenylate cyclase responses (beta-adrenergic-, prostaglandin E-, adenosine-, and histamine (H2)-adenylate cyclase responses) were significantly decreased. These PMA-induced effects on the epidermal adenylate cyclase system were mimicked by 1-oleoyl-2-acetyl-glycerol, a membrane-permeable synthetic diacylglycerol, and by the non-phorbol PKC activator, mezerein. 4-O-methyl PMA, a very weak PKC activator, had no effect on adenylate cyclase responses of the epidermis. The addition of the PKC inhibitor, H-7 (1-(5-isoquinoline-sulfonyl)-2-methyl piperazine dihydrochloride), to the incubation medium significantly inhibited the effect of PMA on forskolin-induced cyclic AMP accumulation. Furthermore, following H-7 treatment, the epidermal receptor-adenylate cyclase responses were significantly increased. These results indicate that PKC modulates epidermal adenylate cyclase responses resulting in an increase in forskolin-induced cyclic AMP accumulation and a decrease in receptor-adenylate cyclase responses of the epidermis.
J Invest Dermatol 1989 Sep
PMID:Effects of the tumor promoter, phorbol 12-myristate, 13-acetate, on the epidermal adenylate cyclase system: evidence for adenylate cyclase-regulation by protein kinase C. 254 24

On the fourth day after a single painting of 2,4,6-trinitro-chlorobenzene on the abdominal skin, inguinal lymph nodes were removed, and a single-cell suspension was prepared. The cells were analyzed flow cytometrically, using monoclonal anti-protein kinase C antibody. It was found that the number of lymph node cells in which protein kinase C was detected on the cell surface was significantly increased over that in non-treated mice (p less than 0.01). On the basis of our results and discussions in the literature, it is thought that protein kinase C is related to the initiation of the contact hypersensitivity reaction.
J Dermatol 1989 Oct
PMID:Flow cytometric analysis of protein kinase C in lymph node cells during the induction phase of contact hypersensitivity reaction. 260 Feb 72

Mitogens, such as polypeptide growth factors and phorbol ester tumor promoters, act by binding to specific receptors and inducing a pleiotropic response in cultured mammalian cells, which results in the induction of cellular proliferation. An early effect of such agents is the inhibition of binding of epidermal growth factor (EGF) to its receptor. Ultraviolet radiation has also been shown to induce a proliferative response in vivo and in vitro and to act as a tumor promoter in animal skin. We, therefore, examined the effect of ultraviolet radiation (UVB - 290-320 nm) on EGF binding to cells in culture. We found that UVB (100-300 J/m2) induced a rapid, dose-dependent inhibition of EGF binding in a mouse fibroblast cell line, which resulted from a decrease in both number and affinity of binding sites. Phosphorylation of the EGF receptor by protein kinase C (PKC) is not likely to be the mechanism for inhibition, since UVB treatment did not result in PKC activation or modulation of phorbol diester binding.
J Invest Dermatol 1989 Apr
PMID:Ultraviolet-B (290-320 nm)-irradiation inhibits epidermal growth-factor binding to mammalian cells. 278 19

The intracellular signal pathways that mediate pigmentation in human skin are unknown. We now report that a diacylglycerol (DAG) analogue 1-oleoyl-2-acetyl-glycerol (OAG) 25-100 microns strikingly increased the melanin content of cultured human melanocytes in a dose dependent manner without altering growth rate. The pigment increase occurred within 24 h, was accompanied by increased incorporation of the melanin precursor L-3,4-dihydroxyphenyl alanine (DOPA), required new protein synthesis, and was completely blocked by the protein kinase C (PKC) inhibitors H-7 and sphingosine. A PKC-inactive DAG isomer had no effect on melanin per cell. These results implicate protein kinase C and its effector DAG in melanogenesis.
J Invest Dermatol 1989 Nov
PMID:Human melanogenesis is stimulated by diacylglycerol. 215 70

L-Serine increased the growth of passaged human foreskin keratinocytes in terms of DNA and protein per dish of cells, and potentiated the mitogenic effects of serum and epidermal growth factor, and also insulin, keratinocyte growth factor, and a bovine pituitary extract. The effects of serine were apparent with as little as 0.05 mM. The stimulatory effects of these various growth factors were additive, without synergism. Exposure to L-[3H]serine resulted in labeling of the phospholipids phosphatidyl (Ptd) serine, Ptd ethanolamine, sphingomyelin, and, to a slight extent, Ptd choline. The time course of labeling suggested synthesis of Ptd serine was initiated; Ptd serine was converted to Ptd ethanolamine; little methylation of Ptd ethanolamine to form Ptd choline took place. Separation of nonradioactive phospholipids and phosphorus assay of individual lipids showed that serine-supplemented cells had only slightly increased content of Ptd serine and Ptd ethanolamine. The significance of these for activation of protein kinase C is discussed.
J Invest Dermatol 1987 Feb
PMID:L-serine potentiates the mitogenic effects of growth factors on cultured human keratinocytes. 310 Jun 54

To investigate the mechanisms responsible for the distinct cutaneous manifestations of erythropoietic protoporphyria and porphyria cutanea tarda, the effects of protoporphyrin (PP) and uroporphyrin (URO), the predominant porphyrins in the respective disease, on mast cells were examined. Release of preformed and generated mediators was assessed by the release of radioactivity from cells labeled with [3H]serotonin and [14C]arachidonic acid, respectively. Clinically relevant doses of PP (25-500 ng/ml) and 396-407 nm irradiation (3-16 X 10(2)J/m2) induced maximal net release of preformed mediators of 44.52 +/- 6.6 to 58.01 +/- 4.0% (mean +/- SE). In contrast, irradiation in the presence of URO (50-5000 ng/ml) resulted in less than 5% net release. [3H]Serotonin release induced by PP and irradiation was calcium-independent, and was not enhanced by phorbol 12-myristate 13-acetate, a known activator of protein kinase C. This release was suppressed by catalase, a scavenger of hydrogen peroxide. Furthermore, irradiation in the presence of PP, but not in the presence of URO, resulted in perturbation of cell membrane. Irradiation in the presence of PP also resulted in a maximal net release of generated mediators of 9.98 +/- 3.5% (mean +/- SE), whereas similar treatment in the presence of URO induced less than 0.5% net release. These results suggested that the burning, stinging, erythema, and edema experienced by patients with erythropoietic protoporphyria following sun exposure, and the lack of such findings in patients with porphyria cutanea tarda, may be explained, at least in part, by the differential effects of PP and URO on mast cells.
J Invest Dermatol 1987 Mar
PMID:Differential effects of protoporphyrin and uroporphyrin on murine mast cells. 310 21

Phosphorylation of mouse epidermal proteins by endogenous protein kinases and production of arachidonic acid are processes stimulated by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate. In mouse epidermal homogenates, each process, as well as production of diacylglycerol (the physiologic activator of protein kinase C), was inhibited by bromophenacyl bromide at concentrations equivalent to those that inhibit tumor promotion. These results lend support to the hypothesis that tumor promotion in mouse skin may be mediated by activation of protein kinase C.
J Invest Dermatol 1985 May
PMID:Tumor promoter-stimulated protein phosphorylation in mouse epidermis is inhibited by bromophenacyl bromide. 315 13


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