PTP1B is a nonreceptor type protein tyrosine phosphatase that has essential roles in insulin and leptin signaling, as well as important functions in growth factor and integrin signaling. The structure of PTP1B includes a conserved phosphatase domain, C-terminal hydrophobic residues for targeting to the cytoplasmic face of the endoplasmic reticulum, and proline-rich regions characteristic of SH3 domain binding motifs. PTP1B can interact with N-Cadherin and dephosphorylate beta-catenin associated with cadherin complexes. PTP1B also interacts with Insulin and EGF receptors, and undergoes phosphorylation after receptor stimulation. Tyrosine phosphorylation at Tyr-66, Tyr-152, and Tyr-153 occurs after insulin receptor activation, and tyrosine phosphorylation of Tyr-152 may be required for interactions with N-Cadherin. In addition, Akt can phosphorylate Ser-50 and this phosphorylation can reduce PTP1B activity.
