Abstract

Epidermal growth factor (EGF), a polypeptide hormone discovered in the mouse, is also present in man. EGF binds to membranes of epithelial cells to produce anabolic effects and proliferative growth in cultured cells at physiologic concentrations. Human EGF will be purified and an antibody raised. Serum levels of EGF will be measured by radioimmunoassay, competitive membrane receptor binding assay, and a sensitive quantitative biological assay. The possible role of EGF in psoriasis and lamellar ichthyosis, disorders with documented hyperproliferative cytokinetics, will be studied by these assays and in cultured cells from patients with special efforts to look for abnormalities in binding or biological response to EGF. Parallel biochemical studies and quantitative comparison of binding with biochemical effects of EGF following binding will be conducted which would be useful in elucidating any abnormality detected by the screening studies of clinical disorders. Possible membrane or cytoplasmic protein phosphorylation by EGF will be sought. Antagonism by cholera toxin of glucose or amino acid transport, phosphofructokinase activation, or other biochemical effects of EGF will be studied. These studies may help elucidate the mechanisms of the biochemical events preceding mitogenesis by EGF.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR025871-08
Application #
3155359
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1979-07-01
Project End
1987-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
8
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

Hu, P; O'Keefe, E J; Rubenstein, D S (2001) Tyrosine phosphorylation of human keratinocyte beta-catenin and plakoglobin reversibly regulates their binding to E-cadherin and alpha-catenin. J Invest Dermatol 117:1059-67
O'Keefe, E J; Hamilton, E H; Lee, S C et al. (1993) Trichohyalin: a structural protein of hair, tongue, nail, and epidermis. J Invest Dermatol 101:65S-71S
Chiu, M L; Jones, J C; O'Keefe, E J (1992) Restricted tissue distribution of a 37-kD possible adherens junction protein. J Cell Biol 119:1689-700
Petersen, M J; Woodley, D T; Stricklin, G P et al. (1992) Synthesis and regulation of keratinocyte collagenase. Matrix Suppl 1:192-7
Hamilton, E H; Sealock, R; Wallace, N R et al. (1992) Trichohyalin: purification from porcine tongue epithelium and characterization of the native protein. J Invest Dermatol 98:881-9
Feldman, S R; O'Keefe, E J (1991) Isolation of a partial clone of desmoplakin-1 by antibody screening of a lambda gt11 library. Am J Med Sci 301:151-6
Hamilton, E H; Payne Jr, R E; O'Keefe, E J (1991) Trichohyalin: presence in the granular layer and stratum corneum of normal human epidermis. J Invest Dermatol 96:666-72
O'Keefe, E; Payne Jr, R E (1991) Minoxidil: inhibition of proliferation of keratinocytes in vitro. J Invest Dermatol 97:534-6
Woodley, D T; Briggaman, R A; Herzog, S R et al. (1990) Characterization of ""neo-dermis"" formation beneath cultured human epidermal autografts transplanted on muscle fascia. J Invest Dermatol 95:20-6
Petersen, M J; Woodley, D T; Stricklin, G P et al. (1990) Enhanced synthesis of collagenase by human keratinocytes cultured on type I or type IV collagen. J Invest Dermatol 94:341-6

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