PKCdelta activation: a divergence point in the signaling of insulin and IGF-1-induced proliferation of skin keratinocytes.
| Autor: | Shen, S, Alt, A, Wertheimer, E, Gartsbein, M, Kuroki, T, Ohba, M, Braiman, L, Sampson, S R, Tennenbaum, T |
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| Předmět: |
ADENOSINE triphosphatase
ANIMAL experimentation BIOCHEMISTRY BIOLOGICAL transport CELL culture CELL division CELLULAR signal transduction COMPARATIVE studies GENES INSULIN ISOENZYMES KERATINOCYTES PHENOMENOLOGY RESEARCH methodology MEDICAL cooperation METALS MICE RESEARCH SOMATOMEDIN TRANSFERASES EVALUATION research |
| Zdroj: | Diabetes; Feb2001, Vol. 50 Issue 2, p255-264, 10p |
| Abstrakt: | Insulin and insulin-like growth factor-1 (IGF-1) are members of the family of the insulin family of growth factors, which activate similar cellular downstream pathways. In this study, we analyzed the effects of insulin and IGF-1 on the proliferation of murine skin keratinocytes in an attempt to determine whether these hormones trigger the same signaling pathways. Increasing doses of insulin and IGF-1 promote keratinocyte proliferation in an additive manner. We identified downstream pathways specifically involved in insulin signaling that are known to play a role in skin physiology; these include activation of the Na+/K+ pump and protein kinase C (PKC). Insulin, but not IGF-1, stimulated Na+/K+ pump activity. Furthermore, ouabain, a specific Na+/K+ pump inhibitor, abolished the proliferative effect of insulin but not that of IGF-1. Insulin and IGF-1 also differentially regulated PKC activation. Insulin, but not IGF-1, specifically activated and translocated the PKCB isoform to the membrane fraction. There was no effect on PKC isoforms alpha, eta, epsilon, and zeta, which are expressed in skin. PKC8 overexpression increased keratinocyte proliferation and Na+/K+ pump activity to a degree similar to that induced by insulin but had no affect on IGF-1-induced proliferation. Furthermore, a dominant negative form of PKCdelta abolished the effects of insulin on both proliferation and Na+/K+ pump activity but did not abrogate induction of keratinocyte proliferation induced by other growth factors. These data indicate that though insulin or IGF-1 stimulation induce keratinocyte proliferation, only insulin action is specifically mediated via PKC8 and involves activation of the Na+/K+ pump. [ABSTRACT FROM AUTHOR] |
| Databáze: | Complementary Index |
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