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Protein‐tyrosine sulfation is required for post‐natal survival in mice
Author(s) -
Westmuckett Andrew D.,
Hoffhines Adam J.,
Moore Kevin L.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb52
Subject(s) - sulfation , biology , tyrosine , gene , medicine , endocrinology , andrology , biochemistry
Tyrosine sulfation is a post‐translational modification mediated by two Golgi tyrosylprotein sulfotransferases (TPST‐1 and −2) expressed in all mammalian cells. Tyrosine sulfation plays an important role in the function of proteins by enhancing protein‐protein interactions. To explore the role of TPSTs in vivo, Tpst1−/−, Tpst2+/− males and females were produced and mated to generate Tpst double knockouts (DKO). These matings were productive (5.0 ± 2.0 pups/litter, n = 82) and DKOs were born at the expected frequency (27%). However, 63% of the DKO pups were found dead the morning after birth (P1), 94% were dead by P5 and none survived beyond P28. To gain insight into the cause of perinatal death, we performed caesarian sections at E19.5 on females from Tpst1−/−, Tpst2+/− and control wild type mating pairs. All wild type pups (n = 13) were born alive, appeared pink and active, and survived for at least 3 hrs. All DKO pups (n = 11) were also born alive, and had normal weight and crown‐to‐rump length. However, 7 of 11 DKO pups showed signs of respiratory distress and/or cyanosis and 4 of 11 died within 3 hrs. To determine if other TPST genes exist, tissues from DKOs were metabolically labeled with Na 35 SO 4 and sulfoamino acid analysis was performed. We failed to detect 35 S‐sulfotyrosine in alkaline hydrolysates of secreted or cellular proteins synthesized by DKO fetal liver and various tissues from a DKO surviving to P20. In conclusion, Tpst1 and Tpst2 are the only tyrosylprotein sulfotransferases expressed in the mouse and protein‐tyrosine sulfation is required for post‐natal survival. Supported by NIH Grant HL74015.