Identification of a variant form of tyrosine phosphatase LYP.
BACKGROUND
Protein tyrosine phosphatases (PTPs) are important cell signaling regulators with major pathological implications. LYP (also known as PTPN22) is an intracellular enzyme initially found to be predominately expressed in lymphocytes. Importantly, an allelic R620W variant of LYP is strongly associated with multiple autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and autoimmune thyroid disease.


RESULTS
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.


CONCLUSIONS
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.
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
Shaofeng
S
Wang
Hongbo
H
Dong
Jiayu
J
Han
Wanting T
WT
Ho
Xueqi
X
Fu
Zhizhuang J
ZJ
Zhao
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D006801:Humans; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000032:analysis / Q000235:genetics / Q000302:isolation & purification; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000032:analysis* / Q000235:genetics* / Q000302:isolation & purification; D016415:Sequence Alignment
D020033:Protein Isoforms; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22