PROTEIN-TYROSINE PHOSPHATASE-1B ACTS AS A NEGATIVE REGULATOR OF INSULIN SIGNAL-TRANSDUCTION

Insulin signaling involves a dynamic cascade of protein tyrosine phosp horylation and dephosphorylation. Most of our understanding of this pr ocess comes from studies focusing on tyrosine kinases, which are signa l activators. Our knowledge of the role of protein-tyrosine phosphatas es (PTPases), signal attenuators, in regulating insulin signal transdu ction remains rather limited. Protein-tyrosine phosphatase 1B (PTP-1B) , the prototypical PTPase, is ubiquitously and abundantly expressed. W ork from several laboratories, including our own, has implicated PTP-1 B as a negative regulator of insulin action and as a potentially impor tant mediator in the pathogenesis of insulin-resistance and non-insuli n dependent diabetes mellitus (NIDDM).