The regulation of receptor protein tyrosine phosphatases by the dimerization of intracellular domains

Protein tyrosine phosphatases (PTPs) are critical in many signal transduction pathways for cell regulation. The activity of PTPs is governed by interactions between various regulatory domains and their partners. Receptor-type PTPs (PTPRs) also have many extracellular regulatory domains. The intracellular domain of some PTPRs consists of D1 and D2 domains, similar to classical PTPs. The D1 domain is an active phosphatase domain, but the D2 domain has weak or no activity. The D2 domain regulates the phosphatase activity of PTPRs containing the D1–D2 domain. Many studies have shown that the dimerization of the D2 domain can inhibit the phosphatase activity of PTPRs. A few models have been proposed to explain how phosphatase activity is inhibited by dimerization, but the precise mechanism is still not established. In this review, we discuss the regulatory mechanism of the phosphatase activity of PTPRs via the intracellular domain.