Recombinant human müllerian inhibiting substance inhibits epidermal growth factor receptor tyrosine kinase.
Autophosphorylation of the epidermal growth factor (EGF) receptor in A-431 cells and plasma membrane fractions was inhibited by partially purified recombinant human Müllerian Inhibiting Substance (MIS). Immunoprecipitation of the EFG receptor using anti-EGF receptor or anti-phosphotyrosine antibodies, and phosphoamino acid analysis of this receptor, demonstrated that MIS specifically inhibited EGF-induced tyrosine phosphorylation. Inhibition of EGF receptor autophosphorylation by MIS in membrane preparations was not affected by increasing concentrations of EGF, manganese or [gamma-(32)P] ATP. Thus, it is unlikely that MIS competes for EGF binding sites or sequesters substrate. Immunoabsorption of MIS with anti-human MIS antibody blocked the MIS inhibition of EGF receptor autophosphorylation, indicating that the inhibition was due to MIS. Our data suggest that MIS regulates the activity of the EGF receptor tyrosine kinase in A-431 cells.
Cigarroa
F G
FG
Pediatric Surgical Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Coughlin
J P
JP
Donahoe
P K
PK
White
M F
MF
Uitvlugt
N
N
MacLaughlin
D T
DT
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D054304:Anti-Mullerian Hormone; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins; D006131:Growth Inhibitors / Q000502:physiology*; D006801:Humans; D009095:Mullerian Ducts / Q000166:cytology; D009924:Organ Culture Techniques; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013735:Testicular Hormones / Q000502:physiology*
D000596:Amino Acids; D006023:Glycoproteins; D006131:Growth Inhibitors; D011994:Recombinant Proteins; D013735:Testicular Hormones; D054304:Anti-Mullerian Hormone; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases