Differential long-term regulation of MEK and of p42 MAPK in rat glomerular mesangial cells.
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.
Schramek
H
H
Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
Sorokin
A
A
Watson
R D
RD
Dunn
M J
MJ
D000818:Animals; D000077214:Becaplermin; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D002417:Cattle / Q000097:blood / Q000196:embryology; D002478:Cells, Cultured; D016232:Endothelins / Q000494:pharmacology; D005312:Fetal Blood / Q000502:physiology; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D013997:Time Factors
D016232:Endothelins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000077214:Becaplermin; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases