Tyrosine kinase inhibitors potentiate the induction of low density lipoprotein receptor gene expression by hepatocyte growth factor.
The role of tyrosine kinase, protein kinase C, cyclic nucleotide- and Ca(2+)-calmodulin-dependent protein kinase second messenger pathways in the induction of LDL receptor gene expression by hepatocyte growth factor (HGF) was studied in the human hepatoma cell line Hep-G2. Incubation with media containing HGF increased the level of LDL receptor mRNA by 6.5-fold. Co-incubation with HGF and either of two tyrosine kinase inhibitors genistein (2.0-20.0 micrograms/ml) and herbimycin A (0.5-500.0 ng/ml) increased the level of LDL receptor mRNA above that observed with HGF alone by 40-60%. Incubation with HGF in the presence of the calmodulin antagonist W7 (10-30 microM) also super-induced the level of LDL receptor mRNA by nearly 230%. The protein kinase C and A inhibitors chelerythrine (0.1-10.0 microM) and H8 (0.5-5.0 microM), respectively, had no significant effects on the induction of LDL receptor mRNA by HGF. Taken together, these data suggest that tyrosine kinase, protein kinases C and A, and Ca(2+)-calmodulin dependent protein kinase activities are not essential for activation of LDL receptor gene expression in Hep-G2 cells by HGF.
D001483:Base Sequence; D005786:Gene Expression Regulation / Q000187:drug effects*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D011973:Receptors, LDL / Q000235:genetics*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D011973:Receptors, LDL; D017228:Hepatocyte Growth Factor; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C