Reduction of epidermal growth factor receptor phosphorylation by activated Mullerian inhibiting substance is vanadate-sensitive.
The carboxy-terminal domain of recombinant human Mullerian inhibiting substance (MIS) inhibits cellular proliferation in vitro and decreases epidermal growth factor (EGF)-dependent phosphorylation of the EGF receptor. Proteolytically cleaved and undissociated MIS is more potent than carboxy-terminal MIS alone, supporting a functional role for the amino-terminal region of the molecule. MIS does not block EGF binding to the EGF receptor, thus, MIS reduction of EGF receptor phosphorylation must occur distal to receptor ligand binding. The effect of proteolytically cleaved MIS on reduction of EGF receptor phosphorylation in membrane preparations is decreased by a specific phosphatase inhibitor, vanadate, thus implicating a membrane phosphatase in this MIS action at the EGF receptor.
Maggard
M A
MA
Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Boston 02114, USA.
Catlin
E A
EA
Hudson
P L
PL
Donahoe
P K
PK
MacLaughlin
D T
DT
D054304:Anti-Mullerian Hormone; D002452:Cell Count; D002453:Cell Cycle; D002462:Cell Membrane / Q000201:enzymology*; D066246:ErbB Receptors / Q000187:drug effects* / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D006023:Glycoproteins; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D009095:Mullerian Ducts / Q000502:physiology*; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D013735:Testicular Hormones / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D006023:Glycoproteins; D006131:Growth Inhibitors; D013735:Testicular Hormones; D054304:Anti-Mullerian Hormone; D010770:Phosphotransferases; D066246:ErbB Receptors; D017027:Protein Tyrosine Phosphatases; D005341:Fibrinolysin