A mutation in Tpst2 encoding tyrosylprotein sulfotransferase causes dwarfism associated with hypothyroidism
| Autor: | Shinya Okano, Tomomi Miyamoto, Ji Ming Cheng, Nobuya Sasaki, Aogu Nagata, Yayoi Hosoda, Ichiro Miyoshi, Atsushi Asano, Takashi Agui, Ming Ding |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Tyrosine sulfation
Tyrosylprotein sulfotransferase Male endocrine system Sulfotransferase medicine.medical_specialty endocrine system diseases Molecular Sequence Data Mutation Missense Dwarfism Thyrotropin Mice Transgenic Biology medicine.disease_cause Thyrotropin receptor Substrate Specificity Mice Endocrinology Internal medicine medicine Congenital Hypothyroidism Missense mutation Animals Amino Acid Sequence Tyrosine Molecular Biology DNA Primers Mutation Base Sequence Sequence Homology Amino Acid Genetic Complementation Test Receptors Thyrotropin General Medicine medicine.disease Molecular biology Mice Mutant Strains Mice Inbred C57BL Phenotype Female Sulfotransferases Protein Processing Post-Translational hormones hormone substitutes and hormone antagonists Signal Transduction |
| Zdroj: | Molecular Endocrinology. 21(7):1713-1721 |
| ISSN: | 0888-8809 |
| Popis: | The growth-retarded (grt) mouse has an autosomal recessive, fetal-onset, severe thyroid hypoplasia related to TSH hyporesponsiveness. Through genetic mapping and complementation experiments, we show that grt is a missense mutation of a highly conserved region of the tyrosylprotein sulfotransferase 2 (Tpst2) gene, encoding one of the two Tpst genes implicated in posttranslational tyrosine O-sulfation. We present evidence that the grt mutation leads to a loss of TPST2 activity, and TPST2 isoform has a high degree of substrate preference for TSH receptor (TSHR). The expression of TPST2 can restore TSH-TSHR-mediated cAMP production in fibroblasts derived from grt mice. Therefore, we propose that the tyrosine sulfation of TSHR by TPST2 is crucial for TSH signaling and resultant thyroid gland function. |
| Databáze: | OpenAIRE |
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