Published in

American Chemical Society, Biochemistry, 3(46), p. 709-719, 2006

DOI: 10.1021/bi061546m

Links

Tools

Export citation

Search in Google Scholar

Reversible Oxidation of the Membrane Distal Domain of Receptor PTPα Is Mediated by a Cyclic Sulfenamide †

This paper is available in a repository.
This paper is available in a repository.

Full text: Download

Green circle
Preprint: archiving allowed
  • Must obtain written permission from Editor
  • Must not violate ACS ethical Guidelines
Orange circle
Postprint: archiving restricted
  • Must obtain written permission from Editor
  • Must not violate ACS ethical Guidelines
Red circle
Published version: archiving forbidden
Data provided by SHERPA/RoMEO

Abstract

Protein tyrosine phosphatases (PTPs) are fundamental to the regulation of cellular signalling cascades triggered by protein tyrosine kinases. Most receptor-like PTPs (RPTPs) comprise two tandem PTP domains, with only the membrane proximal domains (D1) having significant phosphatase activity; the membrane distal domains (D2) display little to no catalytic activity. Intriguingly, however, many RPTP D2s share the catalytically essential Cys and Arg residues of D1s. D2 of RPTPalpha may function as a redox sensor that mediates regulation of D1 via reactive oxygen species. Oxidation of Cys723 of RPTPalpha D2 (equivalent to PTP catalytic Cys residues) stabilizes RPTPalpha dimers, induces rotational coupling, and is required for inactivation of D1 phosphatase activity. Here, we investigated the structural consequences of RPTPalpha D2 oxidation. Exposure of RPTPalpha D2 to oxidants promotes formation of a cyclic sulfenamide species, a reversibly oxidized state of Cys723, accompanied by conformational changes of the D2 catalytic site. The cyclic sulfenamide is highly resistant to terminal oxidation to sulfinic and sulfonic acids. Conformational changes associated with RPTPalpha D2 oxidation have implications for RPTPalpha quaternary structure and allosteric regulation of D1 phosphatase activity.