Protein tyrosine phosphatases, or PTPs, are type I transmembrane proteins, membrane associated proteins or proteins localized in nuclei. Examples of transmembrane PTPs are LAR, PTP alpha, PTP beta, PTP gamma, PTP delta, PTP epsilon, PTP zeta, PTP thet, PTP upsilon and PTPs. Transmembrane PTPsigma play diverse roles during development and in adult tissues. Immunodepletion studies have suggested LAR to be a regulator of insulin receptor phosphorylation. PTP alpha activity is increased twofold in response to phorbol ester stimulation, resulting in serine phosphorylation either directly or indirectly by members of the PKC family. Overexpression of v-H-Ras and Neu, but not Myc or Int2, in mammary tumors has been shown to induce PTPe expression. An alternative splicing event leads to a nervous tissue-specific chondroitin sulfate proteoglycan called phosphacan, which represents the amino terminal portion of PTP omega. PTP thet and PTP?share a conserved amino terminal 160 amino acid MAM domain which facilitates homophilic binding. PTP upsilon localizes to points of cell contact and may be involved in regulating the assembly and disassembly of cadherin/catenin complexes in vivo. PTPsigma contains an extracellular region, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. PTPsigma may also be involved in the molecular control of adult nerve repair. Four alternatively spliced transcript variants, which encode distinct proteins, have been reported.