INVOLVEMENT OF GROWTH-FACTOR RECEPTOR-BOUND PROTEIN-2 IN RAT HEPATOCYTE GROWTH

Citation
S. Wada et al., INVOLVEMENT OF GROWTH-FACTOR RECEPTOR-BOUND PROTEIN-2 IN RAT HEPATOCYTE GROWTH, Journal of gastroenterology and hepatology, 13(6), 1998, pp. 635-642
Citations number
36
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Gastroenterology & Hepatology
ISSN journal
0815-9319
Volume
13
Issue
6
Year of publication
1998
Pages
635 - 642
Database
ISI
SICI code
0815-9319(1998)13:6<635:IOGRPI>2.0.ZU;2-V
Abstract
Growth factor receptor-bound protein-2 (GRB-2) is a protein linking re ceptor tyrosine kinase and Sos (Son of Sevenless gene; Ras GDP/GTP exc hange protein), leading to activation of the Ras-mitogen-activated pro tein kinase (MAPK) cascade. So far, it remains unclear how GRB-2 plays a role in signal transduction pathways evoked by hepatotrophic factor s. This study was attempted to evaluate the involvement, of GRB-2 in s ignalling in rat hepatocyte growth. Using rat cultured hepatocytes sti mulated by hepatotrophic factors and regenerating livers after partial hepatectomy (PH) we examined GRB-2-mediated linkage of hepatotrophic factor receptors to signal transducing molecules such as Sos or dynami n-II by immunoprecipitation and western blot analysis. In primary cult ured hepatocytes stimulated with hepatocyte growth factor (HGF) or epi dermal growth factor (EGF), GRB-2 linked HGF receptor or EGF receptor, respectively, to Sos which activated the mitogen-activated protein ki nase (MAPK) cascade. In contrast, in primary cultured hepatocytes stim ulated with insulin, GRB-2 linked insulin receptor substrate-1 (IRS-1) to dynamin-II as well as Sos. In the early phase after PH, GRB-2 acti vated the Ras-MAPK cascade by linking HGF receptor, IRS-1, or EGF rece ptor to Sos. In the late phase after PH, a complex of IRS-1-GRB-2 asso ciated with dynamin-II, indicating that GRB-2 may transduce signals fr om IRS-1 to dynamin-II. We conclude that GRB-2 may play a role in tran smitting signals from hepatotrophic factors to not only MAPK but also to other signalling pathways in hepatocyte growth.