title: TEC protein tyrosine kinase is involved in the Erk signaling pathway induced by HGF.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pathophysiology, Anhui Medical University, Hefei 230032, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Li
authors.forename: Yinan
authors.initials: Y
authors.lastname: Jiang
authors.forename: Qiping
authors.initials: Q
authors.lastname: Zheng
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Yang
authors.forename: Siying
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006498:Hepatectomy; D017228:Hepatocyte Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D008115:Liver Regeneration; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction
chemical_list: D017228:Hepatocyte Growth Factor; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases