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 re ceptor. Proteolytically cleaved and undissociated MIS is more potent t han carboxy-terminal MIS alone, supporting a functional role for the a mino-terminal region of the molecule. MIS does not block EGF binding t o the EGF receptor, thus, MIS reduction of EGF receptor phosphorylatio n must occur distal to receptor ligand binding, The effect of proteoly tically cleaved MIS on reduction of EGF receptor phosphorylation in me mbrane preparations is decreased by a specific phosphatase inhibitor, vanadate, thus implicating a membrane phosphatase in this MIS action a t the EGF receptor. (C) 1996 by W.B. Saunders Company