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TEC protein tyrosine kinase is involved in the Erk signaling pathway induced by HGF.

Abstract：

BACKGROUND/AIMS:TEC, a member of the TEC family of non-receptor type protein tyrosine kinases, has recently been suggested to play a role in hepatocyte proliferation and liver regeneration. This study aims to investigate the putative mechanisms of TEC kinase regulation of hepatocyte differentiation, i.e. to explore which signaling pathway TEC is involved in, and how TEC is activated in hepatocyte after hepatectomy and hepatocyte growth factor (HGF) stimulation. METHODS:We performed immunoprecipitation (IP) and immunoblotting (IB) to examine TEC tyrosine phosphorylation after partial hepatectomy in mice and HGF stimulation in WB F-344 hepatic cells. The TEC kinase activity was determined by in vitro kinase assay. Reporter gene assay, antisense oligonucleotide and TEC dominant negative mutant (TEC(KM)) were used to examine the possible signaling pathways in which TEC is involved. The cell proliferation rate was evaluated by (3)H-TdR incorporation. RESULTS:TEC phosphorylation and kinase activity were increased in 1 h after hepatectomy or HGF treatment. TEC enhanced the activity of Elk and serum response element (SRE). Inhibition of MEK1 suppressed TEC phosphorylation. Blocking TEC activity dramatically decreased the activation of Erk. Reduced TEC kinase activity also suppressed the proliferation of WB F-344 cells. These results suggest TEC is involved in the Ras-MAPK pathway and acts between MEK1 and Erk. CONCLUSIONS:TEC promotes hepatocyte proliferation and regeneration and is involved in HGF-induced Erk signaling pathway.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Li F,Jiang Y,Zheng Q,Yang X,Wang S

doi

10.1016/j.bbrc.2010.11.068

subject

Has Abstract

pub_date

2011-01-07 00:00:00

pages

79-85

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(10)02127-3

journal_volume

404

pub_type

杂志文章

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