Faculty Collaboration Database

ET-1 and PDGF BB induce MEK mRNA and protein expression in mesangial cells. J Cardiovasc Pharmacol 1995;26 Suppl 3:S95-9

Date

01/01/1995

Pubmed ID

8587480

DOI

10.1097/00005344-199526003-00030

Scopus ID

2-s2.0-0028868573 (requires institutional sign-in at Scopus site)   17 Citations

Abstract

To evaluate a possible mechanism for the chronic regulation of MAPK/ERK kinase-1 (MEK-1) and p42 mitogen-activated protein kinase (MAPK) we studied the long-term effects of 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-1 and p42 MAPK in glomerular mesangial cells (GMCs). ET-1 and PDGF BB led to a time-dependent increase in MEK-1 mRNA expression without altering p42 MAPK mRNA levels. The effect of ET-1 and PDGF BB on MEK-1 mRNA expression was maximal after 24 h (3.3-fold) or 6 h (2.9-fold). Furthermore, the effect of ET-1 and PDGF BB on MEK-1 mRNA expression was additive (4.2-fold after 6 h) and was inhibited by actinomycin D (5 micrograms/ml). Cycloheximide (10 micrograms/ml) inhibited MEK-1 mRNA induction but stimulated p42 MAPK mRNA expression in both the absence and the presence of ET-1 and/or PDGF BB. The ET-1 and PDGF BB-induced increase in MEK-1 mRNA was accompanied by sustained enhancement of both p45 MEK protein expression after 12 h and by elevation of p42 MAPK activity for up to 24 h. We conclude that, in GMCs, MEK-1 acts like a delayed-early gene, whereas p42 MAPK resembles an immediate-early gene. MEK-1 mRNA and protein levels, as well as p42 MAPK activity, can be chronically regulated by both a seven-transmembrane domain receptor-coupled peptide such as ET-1 and by an agonist binding to a receptor with intrinsic protein tyrosine kinase activity, such as PDGF BB.

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
Cycloheximide
Endothelins
Glomerular Mesangium
MAP Kinase Kinase 1
Male
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase Kinases
Platelet-Derived Growth Factor
Protein-Tyrosine Kinases
RNA, Messenger
Rats
Rats, Sprague-Dawley