| Literature DB >> 18981062 |
Valeria Orrú1, Sophia J Tsai, Blanca Rueda, Edoardo Fiorillo, Stephanie M Stanford, Jhimli Dasgupta, Jaana Hartiala, Lei Zhao, Norberto Ortego-Centeno, Sandra D'Alfonso, Frank C Arnett, Hui Wu, Miguel A Gonzalez-Gay, Betty P Tsao, Bernardo Pons-Estel, Marta E Alarcon-Riquelme, Yantao He, Zhong-Yin Zhang, Hooman Allayee, Xiaojiang S Chen, Javier Martin, Nunzio Bottini.
Abstract
A gain-of-function R620W polymorphism in the PTPN22 gene, encoding the lymphoid tyrosine phosphatase LYP, has recently emerged as an important risk factor for human autoimmunity. Here we report that another missense substitution (R263Q) within the catalytic domain of LYP leads to reduced phosphatase activity. High-resolution structural analysis revealed the molecular basis for this loss of function. Furthermore, the Q263 variant conferred protection against human systemic lupus erythematosus, reinforcing the proposal that inhibition of LYP activity could be beneficial in human autoimmunity.Entities:
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Year: 2008 PMID： 18981062 PMCID： PMC2722189 DOI： 10.1093/hmg/ddn363
Source DB: PubMed Journal: Hum Mol Genet ISSN： 0964-6906 Impact factor: 6.150