Faculty Collaboration Database

Endothelins stimulate mitogen-activated protein kinase cascade through either ETA or ETB. Am J Physiol 1994 Oct;267(4 Pt 1):C1130-5

Date

10/01/1994

Pubmed ID

7943276

DOI

10.1152/ajpcell.1994.267.4.C1130

Scopus ID

2-s2.0-0028028402 (requires institutional sign-in at Scopus site)   57 Citations

Abstract

Endothelin (ET) has been shown to activate mitogen-activated protein kinase (MAPK). However, it has been unclear which of the ET receptors is coupled to MAPK activation. In the present study, we conducted experiments to determine which ET receptor is linked to MAPK activation. We found that both human ETA and ETB were coupled to the MAPK cascade in ETA or ETB cDNA-transfected Chinese hamster ovary cells. ET-1 was more potent than ET-3 in the activation of p42 MAPK, induction of MAPK kinase (MAPKK) gel retardation and uptake of [3H]thymidine in ETA-transfected cells, whereas sarafotoxin (S6c) showed no stimulatory effect on the kinases and [3H]thymidine uptake. ET-1, ET-3, and S6c had approximately the same potency to activate p42 MAPK, MAPKK gel retardation, and [3H]thymidine uptake in ETB-transfected cells. These data suggest that 1) ET isopeptides, through either ETA or ETB receptors, induce the MAPK cascade as well as cell proliferation; and 2) the different potencies of ET isopeptides for activation of the MAPK cascade and induction of cell growth are mainly due to their different affinities toward ETA and ETB.

Author List

Wang Y, Rose PM, Webb ML, Dunn MJ

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

Animals
Base Sequence
CHO Cells
Cell Division
Cloning, Molecular
Cricetinae
DNA, Complementary
Endothelins
Enzyme Induction
Humans
Mitogen-Activated Protein Kinase 1
Molecular Sequence Data
Oligonucleotide Probes
Protein-Tyrosine Kinases
Radioligand Assay
Receptors, Endothelin
Recombinant Proteins
Thymidine