Identification of a phosphotyrosyl-protein phosphatase in mouse epidermis.

Binding of epidermal growth factor (EGF) stimulates tyrosyl protein kinase activity of its receptor in the epidermis. This tyrosine residue phosphorylation is thought to be one mechanism by which EGF mediates its effects such as growth stimulation. To modulate a cellular response to EGF, an enzyme which dephosphorylates phosphotyrosyl residues should be present to oppose the effect of the tyrosyl kinase activity of the EGF receptor. We have identified an enzyme in the neonatal mouse epidermis which has the ability to dephosphorylate tyrosyl residues in vitro on EGF receptors. This phosphatase is a soluble protein with a molecular weight greater than 10,000 daltons and shows optimum activity at neutral pH. This epidermal tyrosyl protein phosphatase is not inhibited by tartrate, ATP, and micromolar levels of zinc, but is inhibited by millimolar levels of zinc, magnesium, manganese, and fluoride. Unlike other well-known phosphotyrosyl phosphatases, alkaline phosphatase, and calcineurin, this enzyme is not inhibited by EDTA. Thus, we have identified and partially characterized a possibly unique phosphotyrosyl phosphatase from the epidermis.