First Author | Sasaki N | Year | 2007 |
Journal | Mol Endocrinol | Volume | 21 |
Issue | 7 | Pages | 1713-21 |
PubMed ID | 17456791 | Mgi Jnum | J:122398 |
Mgi Id | MGI:3714232 | Doi | 10.1210/me.2007-0040 |
Citation | Sasaki N, et al. (2007) A mutation in tpst2 encoding tyrosylprotein sulfotransferase causes dwarfism associated with hypothyroidism. Mol Endocrinol 21(7):1713-21 |
abstractText | 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. |