Differential long-term regulation of mitogen-activated protein kinase kinase (mapkk or mek) and of p42 mapk in rat glomerular mesangial cells. Schramek, Herbert, Andrey Sorokin, Roger D. Watson, and Michael J. Dunn. Departments of Medicine and of Physiology and Biophysics, Case Western Reserve University, Division of Nephrology, University Hospitals, Cleveland, Ohio 44106.
APStracts 2:0255C, 1995.
Differential long-term regulation of mitogen-activated protein kinase kinase (MAPKK or MEK) and of p42 MAPK in rat glomerular mesangial cells. - Constitutive stimulation of the mitogen-activated protein kinase (MAPK) activator MEK is sufficient to promote long-term events like cell differentiation, proliferation or transformation. To evaluate a possible mechanism for the chronic regulation of MEK and p42 MAPK we studied the long-term effects of fetal bovine serum (FBS), the G protein-coupled receptor agonist endothelin-1 (ET-1) and the protein tyrosine kinase-coupled receptor agonist platelet-derived growth factor BB (PDGF BB) on MEK and p42 MAPK in glomerular mesangial cells (GMC). FBS, ET-1 and PDGF BB led to a time-dependent increase in MEK-1 mRNA and protein expression without altering p42 MAPK mRNA and protein levels. FBS also induced MEK-1 mRNA expression in diverse cell types including NIH-3T3 fibroblasts, A7r5 vascular smooth muscle cells and Chinese Hamster Ovary (CHO) cells. In GMC, cycloheximide inhibited MEK-1 mRNA induction but stimulated p42 MAPK mRNA expression in both the absence and presence of FBS, ET-1 or PDGF. The FBS-induced increase in MEK-1 mRNA was accompanied by a sustained enhancement of both MEK activity, as assessed by the ability of immunoprecipitated p45 MEK to activate recombinant p42 MAPK and hence phosphorylate myelin basic protein (MBP), and p42 MAPK activity. We conclude that, in GMC, MEK-1 acts like an delayed-early gene and that it can be chronically induced at the mRNA and protein level. 

Received 14 February 1995; accepted in final form 6 July 1995.
APS Manuscript Number C85-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 18 July 1995.