Primary structure of rat hepatocyte growth factor receptor and
induced expression in glomerular mesangial cells.
Liu, Youhua, Evelyn M. Tolbert, Adam M. Sun, and Lance D. Dworkin.
Department of Medicine, Division of Renal diseases, Rhode Island
Hospital, Brown University School of Medicine, Providence, Rhode
Island 02903
APStracts 3:0106F, 1996.
The c-met proto-oncogene encodes a transmembrane tyrosine kinase
receptor for hepatocyte growth factor (HGF). It has been widely
suggested that HGF and its receptor constitute a paracrine signaling
system, in which mesenchymally-derived cells produce ligand that
binds to the receptor predominantly expressed on cells of epithelial
origin. In this study, we have isolated and completely sequenced the
entire coding region of c-met cDNA from the rat kidney. The
nucleotide sequence of the rat c-met cDNA revealed that the HGF
receptor is encoded within single open reading frame as a 190 kDa of
transmembrane glycoprotein consisting of 1382 amino acids.
Determination of c-met mRNA levels in various tissues revealed a
widespread expression of c-met with the highest levels in kidney,
lung and liver. We found simultaneous induction of both HGF and its
receptor gene expression by interleukin-6 (IL-6) in primary cultured
rat glomerular mesangial cells. The expression of HGF and c-met was
remarkably stimulated following incubation of rat mesangial cells
with IL-6, in a time- and dose-dependent manner. Our data suggest
that autocrine action of HGF may be achieved in vivo through
simultaneous stimulation of both HGF and its receptor expression in
renal mesenchymal cells.
Received 19 January 1996; accepted in final form 30 May 1996.
APS Manuscript Number F20-6.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 June 96