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Increased activation of Ras in psoriatic lesions.
- Source :
-
Skin pharmacology and applied skin physiology [Skin Pharmacol Appl Skin Physiol] 1999 Jan-Apr; Vol. 12 (1-2), pp. 90-7. - Publication Year :
- 1999
-
Abstract
- Ras functions as an essential upstream regulator of growth-factor-receptor-coupled signal transduction pathways. Ras is converted from an inactive GDP-bound state to an active GTP-bound state in response to receptor activation. Thus, the ratio of GTP/GDP bound to Ras is a measure of its state of activation. Mutations that stabilize the GTP-bound form of Ras result in constitutive activation and cellular transformation. The most widely used method for measuring Ras activation utilizes [32P]PO4 to label cellular nucleotide pools and is therefore limited to use with cultured cells. We have modified and adapted an enzyme-based method for rapid, precise measurement of Ras-bound GTP and GDP in normal and psoriatic human skin. This method does not require radiolabeling of cellular nucleotides. In cultured fibroblasts, the enzymatic and [32P]PO4 incorporation methods yielded similar results. Application of the enzymatic method to human skin revealed that 6% of Ras was in the active GTP-bound state in normal skin, compared to 15.4% of Ras in psoriatic lesions. The total amount of Ras normalized to protein content was similar in normal and psoriatic skin. Enhanced activation of Ras is likely a critical mediator of the increased cell growth characteristic of psoriatic lesions.
- Subjects :
- Animals
Cell Culture Techniques
Cricetinae
Embryo, Mammalian cytology
Female
Guanosine Diphosphate analysis
Guanosine Triphosphate analysis
Humans
Phosphotransferases physiology
Precipitin Tests
Pregnancy
Signal Transduction
Fibroblasts physiology
Psoriasis metabolism
Receptors, Growth Factor physiology
Skin growth & development
ras Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-2868
- Volume :
- 12
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- Skin pharmacology and applied skin physiology
- Publication Type :
- Academic Journal
- Accession number :
- 10325588
- Full Text :
- https://doi.org/10.1159/000029850