title: A mutation in Tpst2 encoding tyrosylprotein sulfotransferase causes dwarfism associated with hypothyroidism.
abstract: 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.
authors: Laboratory of Experimental Animal Science, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors: Nobuya
authors: N
authors: Sasaki
authors: Yayoi
authors: Y
authors: Hosoda
authors: Aogu
authors: A
authors: Nagata
authors: Ming
authors: M
authors: Ding
authors: Ji-Ming
authors: JM
authors: Cheng
authors: Tomomi
authors: T
authors: Miyamoto
authors: Shinya
authors: S
authors: Okano
authors: Atsushi
authors: A
authors: Asano
authors: Ichiro
authors: I
authors: Miyoshi
authors: Takashi
authors: T
authors: Agui
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003409:Congenital Hypothyroidism / Q000150:complications / Q000201:enzymology* / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D004392:Dwarfism / Q000150:complications / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D005816:Genetic Complementation Test; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010641:Phenotype; D011499:Protein Processing, Post-Translational; D011989:Receptors, Thyrotropin / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013379:Substrate Specificity; D015238:Sulfotransferases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D013972:Thyrotropin / Q000378:metabolism
chemical_list: D017931:DNA Primers; D011989:Receptors, Thyrotropin; D013972:Thyrotropin; D015238:Sulfotransferases; C039079:protein-tyrosine sulfotransferase