Inhibition of tyrosine kinase activity abolishes anabolic and mitogenic effects of prolactin and growth hormone in Nb2 cells.
The effect of genistein, a specific tyrosine kinase inhibitor, on intermediate and long-term effects of lactogen (growth hormone and prolactin) in Nb2 cells has been examined. Genistein inhibited hormone-induced protein and DNA synthesis and mitogenesis in a concentration-dependent manner with an IC50 ranging from 10 to 13 uM. Tyrosine kinase activity was rapidly stimulated by prolactin and was completely blocked by 25 uM genistein. These results demonstrate that lactogen-mediated effects distal to ligand receptor interaction are coupled by tyrosine kinase(s) and suggest that this enzyme activity may be critically involved in the signal transduction mechanism of lactogens.
Carey
G B
GB
Department of Biochemistry and Molecular Biophysics, Medical College of Virginia, Virginia Commomwealth University, Richmond 23298-0614.
Liberti
J P
JP
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D005260:Female; D019833:Genistein; D013006:Growth Hormone / Q000502:physiology*; D007529:Isoflavones / Q000494:pharmacology*; D011388:Prolactin / Q000502:physiology*; D014176:Protein Biosynthesis; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011506:Proteins / Q000187:drug effects; D051381:Rats
D007529:Isoflavones; D011506:Proteins; D011388:Prolactin; D013006:Growth Hormone; D004247:DNA; D019833:Genistein; D011505:Protein-Tyrosine Kinases