Hepatocyte growth factor-induced signal transduction in two normal mouse epithelial cell lines.
We have investigated HGF-induced signal transduction in two normal mouse epithelial cell lines (M23 and MM55). Both cell lines display HGF-induced mitogenesis and high level HGF-induced autophosphorylation of MET/HGFR. In both M23 and MM55 cells, HGF induces association with MET/HGFR and increased tyrosine phosphorylation of the SH2-domain containing proteins PI3K, GAP and NCK. PLC-gamma exhibited neither HGF-induced increases in tyrosine phosphorylation nor an association with MET/HGFR in these cell lines. Additionally, HGF induced increased transcription of c-fos, c-jun, junB, junD, and c-myc early response genes in both cell lines. We therefore suggest that the second messenger proteins PI3K, GAP and NCK, and possibly the protein products of the c-fos, c-jun, junB, junD and c-myc genes, are important elements in the HGF-induced mitogenic pathway in the normal mouse epithelial cell lines M23 and MM55.
Johnson
M
M
Rush Medical School, Department of Biochemistry, Chicago, Illinois 60610, USA.
Kochhar
K
K
Nakamura
T
T
Iyer
A
A
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D017781:Genes, Immediate-Early; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D051379:Mice; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis*; D015290:Second Messenger Systems; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics
D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases