Webbläsaren som du använder stöds inte av denna webbplats. Alla versioner av Internet Explorer stöds inte längre, av oss eller Microsoft (läs mer här: * https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Var god och använd en modern webbläsare för att ta del av denna webbplats, som t.ex. nyaste versioner av Edge, Chrome, Firefox eller Safari osv.

Superresolution imaging of the cytoplasmic phosphatase PTPN22 links integrin-mediated T cell adhesion with autoimmunity

In English

Författare

  • Garth L. Burn
  • Georgina H. Cornish
  • Kasia Potrzebowska
  • Malin Samuelsson
  • Juliette Griffié
  • Sophie Minoughan
  • Mark Yates
  • George Ashdown
  • Nicolas Pernodet
  • Vicky L. Morrison
  • Cristina Sanchez-Blanco
  • Harriet Purvis
  • Fiona Clarke
  • Rebecca J. Brownlie
  • Timothy J. Vyse
  • Rose Zamoyska
  • Dylan M. Owen
  • Lena M. Svensson
  • Andrew P. Cope
Visa allt

Summary, in English

Integrins are heterodimeric transmembrane proteins that play a fundamental role in the migration of leukocytes to sites of infection or injury. We found that protein tyrosine phosphatase nonreceptor type 22 (PTPN22) inhibits signaling by the integrin lymphocyte function-associated antigen-1 (LFA-1) in effector T cells. PTPN22 colocalized with its substrates at the leading edge of cells migrating on surfaces coated with the LFA-1 ligand intercellular adhesion molecule-1 (ICAM-1). Knockout or knockdown of PTPN22 or expression of the autoimmune disease-associated PTPN22-R620W variant resulted in the enhanced phosphorylation of signaling molecules downstream of integrins. Superresolution imaging revealed that PTPN22-R620 (wild-type PTPN22) was present as large clusters in unstimulated T cells and that these disaggregated upon stimulation of LFA-1, enabling increased association of PTPN22 with its binding partners at the leading edge. The failure of PTPN22-R620W molecules to be retained at the leading edge led to increased LFA-1 clustering and integrin-mediated cell adhesion. Our data define a previously uncharacterized mechanism for fine-tuning integrin signaling in T cells, as well as a paradigm of auto-immunity in humans in which disease susceptibility is underpinned by inherited phosphatase mutations that perturb integrin function. 2016

Avdelning/ar

  • Leukocyte Migration

Publiceringsår

2016-10-04

Språk

Engelska

Publikation/Tidskrift/Serie

Science Signaling

Volym

9

Issue

448

Dokumenttyp

Artikel i tidskrift

Förlag

American Association for the Advancement of Science (AAAS)

Ämne

  • Cell and Molecular Biology

Status

Published

Forskningsgrupp

  • Leukocyte Migration

ISBN/ISSN/Övrigt

  • ISSN: 1945-0877