The autoimmunity risk variant LYP-W620 cooperates with CSK in the regulation of TCR signaling.

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.

• Authors: María Luisa de la Puerta, Antonio G Trinidad, María del Carmen Rodríguez, José María de Pereda, Mariano Sánchez Crespo, Yolanda Bayón, Andrés Alonso
• Journal: PloS one (PLoS One) Vol. 8 Issue 1 Pg. e54569 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23359562 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Antigen, T-Cell
• CSK Tyrosine-Protein Kinase
• src-Family Kinases
• CSK protein, human
• Protein Tyrosine Phosphatases

Topics

• Autoimmune Diseases (genetics)
• Autoimmunity
• CSK Tyrosine-Protein Kinase
• Electrophoresis, Polyacrylamide Gel
• Flow Cytometry
• HEK293 Cells
• Humans
• Immunohistochemistry
• Jurkat Cells
• Models, Molecular
• Phosphorylation
• Polymorphism, Single Nucleotide
• Protein Binding
• Protein Tyrosine Phosphatases (genetics, physiology)
• Receptors, Antigen, T-Cell (metabolism)
• Signal Transduction (physiology)
• src-Family Kinases (physiology)