REGULATION OF AN HEPATIC LOW-M(R) MEMBRANE-ASSOCIATED PROTEIN-TYROSINE PHOSPHATASE

Protein-tyrosine phosphatases (PTPases), active against autophosphoryl ated insulin and epidermal growth factor (EGF) receptors in rat liver, are predominantly membrane associated. Fasting of rats for 48 h decre ased hepatic particulate PTPase activity by 15.0-26.9%. This reduction in particulate PTPase activity was due to a rather specific decrease in activity of > 85% of a single species of PTPase, termed PTPase I. D isappearance of PTPase I activity from the particulate fraction was no t accounted for by its translocation to the cytosol. PTPase I displaye d the highest activity against autophosphorylated insulin and EGF rece ptors, relative to activity against a P-32-labelled peptide substrate. of three PTPases resolved from the liver particulate fraction. The M( r) value of PTPase I, as determined by gel filtration on a Superose 12 column was approx. 42000, indicating that PTPase I belongs to the low -M(r) class of PTPases. An antibody raised against PTPase 1B, the prot otype of this class of PTPases, did not react with PTPase I in Western blots. The potential importance of the novel change in activity of PT Pase I in the regulation of insulin-receptor signal transduction is di scussed.