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Dimerization in vivo and inhibition of the nonreceptor form of protein tyrosine phosphatase epsilon.

Abstract：

:cyt-PTP epsilon is a naturally occurring nonreceptor form of the receptor-type protein tyrosine phosphatase (PTP) epsilon. As such, cyt-PTP epsilon enables analysis of phosphatase regulation in the absence of extracellular domains, which participate in dimerization and inactivation of the receptor-type phosphatases receptor-type protein tyrosine phosphatase alpha (RPTPalpha) and CD45. Using immunoprecipitation and gel filtration, we show that cyt-PTP epsilon forms dimers and higher-order associations in vivo, the first such demonstration among nonreceptor phosphatases. Although cyt-PTP epsilon readily dimerizes in the absence of exogenous stabilization, dimerization is increased by oxidative stress. Epidermal growth factor receptor stimulation can affect cyt-PTP epsilon dimerization and tyrosine phosphorylation in either direction, suggesting that cell surface receptors can relay extracellular signals to cyt-PTP epsilon, which lacks extracellular domains of its own. The inactive, membrane-distal (D2) phosphatase domain of cyt-PTP epsilon is a major contributor to intermolecular binding and strongly interacts in a homotypic manner; the presence of D2 and the interactions that it mediates inhibit cyt-PTP epsilon activity. Intermolecular binding is inhibited by the extreme C and N termini of D2. cyt-PTP epsilon lacking these regions constitutively dimerizes, and its activities in vitro towards para-nitrophenylphosphate and in vivo towards the Kv2.1 potassium channel are markedly reduced. We conclude that physiological signals can regulate dimerization and phosphorylation of cyt-PTP epsilon in the absence of direct interaction between the PTP and extracellular molecules. Furthermore, dimerization can be mediated by the D2 domain and does not strictly require the presence of PTP extracellular domains.

journal_name

Mol Cell Biol

journal_title

Molecular and cellular biology

authors

Toledano-Katchalski H,Tiran Z,Sines T,Shani G,Granot-Attas S,den Hertog J,Elson A

doi

10.1128/mcb.23.15.5460-5471.2003

subject

Has Abstract

pub_date

2003-08-01 00:00:00

pages

5460-71

issue

eissn

0270-7306

issn

1098-5549

journal_volume

pub_type

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Dimerization in vivo and inhibition of the nonreceptor form of protein tyrosine phosphatase epsilon.