Faculty Collaboration Database

Differential long-term regulation of MEK and of p42 MAPK in rat glomerular mesangial cells. Am J Physiol 1996 Jan;270(1 Pt 1):C40-8

Date

01/01/1996

Pubmed ID

8772428

DOI

10.1152/ajpcell.1996.270.1.C40

Scopus ID

2-s2.0-0030065094 (requires institutional sign-in at Scopus site)   25 Citations

Abstract

Constitutive stimulation of the mitogen-activated protein kinase (MAPK) activator MAPK/ERK kinase (MEK) is sufficient to promote long-term events such as cell differentiation, proliferation, and 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 cells. In GMC, cycloheximide inhibited MEK-1 mRNA induction but stimulated p42 MAPK mRNA expression in 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 MEK activity, as assessed by the ability of immunoprecipitated p45 MEK to activate recombinant p42 MAPK and hence phosphorylate myelin basic protein, and p42 MAPK activity. We conclude that, in GMC, MEK-1 acts like a delayed-early gene and that it can be chronically induced at the mRNA and protein level.

Author List

Schramek H, Sorokin A, Watson RD, Dunn MJ

Author

Andrey Sorokin PhD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Calcium-Calmodulin-Dependent Protein Kinases
Cattle
Cells, Cultured
Endothelins
Fetal Blood
Glomerular Mesangium
Male
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase Kinases
Platelet-Derived Growth Factor
Protein Kinases
Protein-Tyrosine Kinases
Proto-Oncogene Proteins c-sis
RNA, Messenger
Rats
Rats, Sprague-Dawley
Recombinant Proteins
Time Factors