The Autoimmunity Risk Variant LYP-W620 Cooperates with CSK in the Regulation of TCR Signaling
Open Access
- 24 January 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (1), e54569
- https://doi.org/10.1371/journal.pone.0054569
Abstract
The protein tyrosine phosphatase LYP, a key regulator of TCR signaling, presents a single nucleotide polymorphism, C1858T, associated with several autoimmune diseases such as type I diabetes, rheumatoid arthritis, and lupus. This polymorphism changes an R by a W in the P1 Pro rich motif of LYP, which binds to CSK SH3 domain, another negative regulator of TCR signaling. Based on the analysis of the mouse homologue, Pep, it was proposed that LYP and CSK bind constitutively to inhibit LCK and subsequently TCR signaling. The detailed study of LYP/CSK interaction, here presented, showed that LYP/CSK interaction was inducible upon TCR stimulation, and involved LYP P1 and P2 motifs, and CSK SH3 and SH2 domains. Abrogating LYP/CSK interaction did not preclude the regulation of TCR signaling by these proteins.This publication has 39 references indexed in Scilit:
- LYP inhibits T-cell activation when dissociated from CSKNature Chemical Biology, 2012
- Autoimmune-associated PTPN22 R620W Variation Reduces Phosphorylation of Lymphoid Phosphatase on an Inhibitory Tyrosine ResidueOnline Journal of Public Health Informatics, 2010
- PTPN22 Deficiency Cooperates with the CD45 E613R Allele to Break Tolerance on a Non-Autoimmune BackgroundThe Journal of Immunology, 2009
- Characterization of New Substrates Targeted By Yersinia Tyrosine Phosphatase YopHPLOS ONE, 2009
- Structural Basis for the Recognition of c-Src by Its Inactivator CskCell, 2008
- Deletion of the LIME adaptor protein minimally affects T and B cell development and functionEuropean Journal of Immunology, 2007
- Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variantNature Genetics, 2005
- SH2 Domain-Mediated Interaction of Inhibitory Protein Tyrosine Kinase Csk with Protein Tyrosine Phosphatase-HSCFMolecular and Cellular Biology, 2001
- Sequence and structure-based prediction of eukaryotic protein phosphorylation sitesJournal of Molecular Biology, 1999
- Negative regulation of T-cell receptor signalling by tyrosine protein kinase p50cskNature, 1993