Regulation of an hepatic low-M(r) membrane-associated protein-tyrosine phosphatase.

Protein-tyrosine phosphatases (PTPases), active against autophosphorylated insulin and epidermal growth factor (EGF) receptors in rat liver, are predominantly membrane associated. Fasting of rats for 48 h decreased 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. Disappearance of PTPase I activity from the particulate fraction was not accounted for by its translocation to the cytosol. PTPase I displayed the highest activity against autophosphorylated insulin and EGF receptors, relative to activity against a 32P-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. 42,000, indicating that PTPase I belongs to the low-M(r) class of PTPases. An antibody raised against PTPase 1B, the prototype of this class of PTPases, did not react with PTPase I in Western blots. The potential importance of the novel change in activity of PTPase I in the regulation of insulin-receptor signal transduction is discussed.