Identification of a variant form of tyrosine phosphatase LYP

In this study, we isolated a novel isoform of LYP designated LYP3. LYP3 differs from LYP1, the known isoform of LYP, in that it lacks a 28 amino acid segment right after the R620W site embedded in a proline-rich protein-protein interaction motif. Genomic sequence analysis revealed that LYP3 resulted from alternative splicing of the LYP gene located on chromosome 1p 13.3-13.1. Reverse transcription PCR analyses of 48 human tissues demonstrated that both LYP1 and LYP3 are predominantly expressed in primary and secondary lymphoid tissues but the relative expression levels of the two isoforms varies in different human tissues and individuals.We thus identified a new variant form of LYP and conducted a comprehensive analysis of LYP tissue expressions. Considering the pathogenesis of LYP R620W, we believe that the expression of LYP3 may have an important role in regulating activity and function of LYP and may be implicated in autoimmune diseases.Protein tyrosine phosphatases (PTPs) act in a coordinated manner with protein tyrosine kinases to control cell signaling thereby regulating various physiological processes [1]. Malfunctioning of these enzymes has major pathological implications. One of the best known examples is the allelic variant of the lymphoid tyrosine phosphatase LYP (PTPN22) which is associated with multiple autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and autoimmune thyroid disease [2,3].LYP is a cytoplasmic enzyme belonging to the PEST group of non-receptor classical PTPs [4]. It contains 807 amino acid residues. The murine ortholog of LYP is called PEP [5]. LYP and PEP share 89% and 61% sequence identity in their PTP domains and noncatalytic portions, respectively. The N-terminal part of LYP/PEP contains the catalytic domain conserved in all classical PTPs. The structure of the sequence following the catalytic domain is largely undefined. The last 200 amino acid segment contains 4 proline-rich sequenc