Characterization of Two Distinct Dual Specificity Phosphatases Encoded in Alternative Open Reading Frames of a Single Gene Located on Human Chromosome 10q22.2
Dual specificity phosphatases (DSPs) are members of the protein-tyrosine phosphatase superfamily that dephosphorylate both phosphotyrosine and phosphoserine/threonine residues in vitro . Many DSPs have been found to play important roles in various aspects of cellular function and to be involved in h...
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Published in | The Journal of biological chemistry Vol. 279; no. 40; pp. 41404 - 41413 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Biochemistry and Molecular Biology
01.10.2004
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Subjects | |
Online Access | Get full text |
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Summary: | Dual specificity phosphatases (DSPs) are members of the protein-tyrosine phosphatase superfamily that dephosphorylate both
phosphotyrosine and phosphoserine/threonine residues in vitro . Many DSPs have been found to play important roles in various aspects of cellular function and to be involved in human disease.
We have identified a gene located on human chromosome 10q22.2, which utilizes alternative open reading frames (ORFs) to encode
the following two distinct DSPs: the previously described testis and skeletal m uscle-specific d ual specificity p hosphatase (TMDP) and a novel DSP, m uscle-restricted d ual s pecificity p hosphatase (MDSP). Use of alternative ORFs encoding distinct proteins from a single gene is extremely rare in eukaryotes,
and in all previously reported cases the two proteins produced from one gene are unrelated. To our knowledge this is the first
example of a gene from which two distinct proteins of the same family are expressed using alternative ORFs. Here we provide
evidence that both MDSP and TMDP proteins are expressed in vivo and are restricted to specific tissues, skeletal muscle and testis, respectively. Most interestingly, the protein expression
profiles of both MDSP and TMDP during mouse postnatal development are strikingly similar. MDSP is expressed at very low levels
in myotubes and early postnatal muscle. TMDP is not detectable in testis lysate in the first 3 weeks of life. The expression
of both MDSP and TMDP proteins was markedly increased at approximately the 3rd week after birth and continued to increase
gradually into adulthood, implying that the physiological functions of both DSPs are specific to the mature/late-developing
organs. The conserved gene structure and the similarity in postnatal expression profile of these two proteins suggest biological
significance of the unusual gene arrangement. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M405286200 |