Müllerian inhibiting substance blocks autophosphorylation of the EGF receptor by inhibiting tyrosine kinase.
The fetal regressor Müllerian inhibiting substance (MIS), in concentrations as low as picomolar, inhibited the growth of A-431 cells and the autophosphorylation of its epidermal growth factor (EGF) receptor. The inhibition of membrane phosphorylation was due neither to the reduction of the total number of EGF receptor binding sites, nor to stimulation of intrinsic phosphates, but rather to inhibition of tyrosine kinase activity. MIS control of EGF receptor autophosphorylation by tyrosine kinase may be one mechanism by which Müllerian duct regression in the embryo and the inhibition of A-431 proliferation is initiated. In addition, MIS as an inhibitor of phosphorylation may furnish a tool to probe the role of membrane phosphorylation in growth control.
D000818:Animals; D054304:Anti-Mullerian Hormone; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins; D006131:Growth Inhibitors; D006801:Humans; D008297:Male; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013735:Testicular Hormones / Q000494:pharmacology*; D014846:Vulvar Neoplasms
D006023:Glycoproteins; D006131:Growth Inhibitors; D013735:Testicular Hormones; D004815:Epidermal Growth Factor; D054304:Anti-Mullerian Hormone; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D010744:Phosphoric Monoester Hydrolases