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 family of protein kinase C (PKC) isoenzymes plays a fundamental part in signal transduction, and thereby regulates important cellular functions, including growth, differentiation, cytokine production and adhesion molecule expression. In lesional psoriatic skin, Ca(2+)-dependent PKC activity, PKC-beta protein and epidermal Langerhans cell (LC) PKC-beta immunostaining are significantly decreased, indicating activation and subsequent down-regulation of PKC. Whether these changes occur in other inflammatory/hyperplastic dermatoses is, however, unknown. We examined PKC-alpha and PKC-beta expression in normal skin, psoriasis, cutaneous T-cell lymphoma (CTCL), lamellar ichthyosis, non-bullous ichthyosiform erythroderma, atopic dermatitis, urushiol-induced allergic contact dermatitis, and sodium lauryl sulphate (SLS)-induced irritant contact dermatitis. Cryostat sections were stained for PKC-alpha and PKC-beta, and the LC marker CD1a, using an immunoperoxidase technique and specific monoclonal antibodies. Double-labelling studies, in normal skin, revealed co-expression of PKC-beta and CD1a by epidermal LCs. Analysis of the number of PKC-beta+ and CD1a+ epidermal LCs, in diseased compared with normal skin, revealed three categories: (i) in psoriasis and CTCL, the PKC-beta+ epidermal LC number was significantly reduced, whereas the CD1a+ epidermal LC number was unchanged; (ii) in allergic and irritant contact dermatitis, both PKC-beta+ and CD1a+ epidermal LCs were significantly reduced in number; and (iii) in atopic dermatitis, the PKC-beta+ epidermal LC number was normal, and CD1a+ epidermal LCs were significantly increased in number. Moreover, the ratio of epidermal LC PKC+/CD1a+ was reduced in all the dermatoses studied, suggesting activation of PKC-beta, with subsequent down-regulation. Within the dermis, increased PKC-beta staining of infiltrating cells was observed in all the conditions studied except lamellar ichthyosis and non-bullous ichthyosiform erythroderma. These data indicate that: (i) down-regulation of LC PKC-beta occurs in a variety of inflammatory and hyperplastic skin disorders, and is not unique to psoriasis, and (ii) the pattern of epidermal LC PKC-beta and CD1a expression varies among the diseases studied. In mice, PKC activation induces LC migration. Thus, down-regulation of epidermal LC PKC-beta associated with reduced CD1a+ epidermal LCs in allergic and irritant contact dermatitis suggests that PKC-beta may transduce the signal for migration of LCs from human epidermis.
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PMID:Down-regulation of Langerhans cell protein kinase C-beta isoenzyme expression in inflammatory and hyperplastic dermatoses. 754 80

Transglutaminase 1 (TGase 1) is expressed during the terminal differentiation of keratinized squamous epithelium to form cornified cell envelope in differentiated keratinocytes by the epsilon-(gamma-glutamyl) cross-linking reaction. The gene for human TGase 1 is responsible for autosomal recessive lamellar ichthyosis, a severe hereditary keratinizing disorder of the skin. We examined the transcriptional activity of the gene in FRSK, rat keratinocytic cells, transfected with the luciferase reporter gene under control of the 5' upstream region of human TGase 1 gene. Transfection of the reporter gene with an expression vector for the eta isoform of novel protein kinase C (nPKCeta), as well as exposure to 12-0-tetradecanoylphorbol-13-acetate, markedly increased the luciferase activity in FRSK, but not in HT-1080 fibrosarcoma cells, although exogenous nPKCeta was expressed in both. The induction was suppressed by deleting the TGase 1 upstream sequence from -95 to -67 and by deleting the kinase domain from exogenous nPKCeta. In comparison with other PKC isoforms, nPKCeta most effectively induced the luciferase activity. We suggest that nPKCeta, an epithelium-specific isoform of PKC, mediates the activation of the TGase 1 transcription.
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PMID:The eta isoform of protein kinase C mediates transcriptional activation of the human transglutaminase 1 gene. 862 60