Sulfated Tyrosines of Thyroglobulin Are Involved in Thyroid Hormone Synthesis

Nlend, Marie; Cauvi, David M.; Venot, Nicole; Chabaud, Odile

doi:10.1006/bbrc.1999.1173

Cited by 18 publications

(10 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies in porcine thyrocytes indicate that the stoichiometry of Tg tyrosine sulfation falls in response to TSH stimulation (Nlend et al, 1999b), that in vitro production of thyroid hormone from Tg is decreased when sulfation is inhibited pharmacologically (Nlend et al, 1999a), and that Tyr 5 , a hormonogenic tyrosine residue in porcine Tg, can be tyrosine-sulfated. However, the precise role of Tg tyrosine sulfation in thyroid hormone synthesis remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Early postnatal pulmonary failure and primary hypothyroidism in mice with combined TPST-1 and TPST-2 deficiency

Westmuckett

Hoffhines

Borghei

et al. 2008

General and Comparative Endocrinology

View full text Add to dashboard Cite

Protein-tyrosine sulfation is a post-translational modification of an unknown number of secreted and membrane proteins mediated by two known Golgi tyrosylprotein sulfotransferases (TPST-1 and TPST-2). Tpst double knockouts were generated to investigate the importance of tyrosine sulfation in vivo. Double knockouts were born alive at the expected frequency, were normal in size, and their tissues do not synthesize sulfotyrosine. However, most pups die in the early postnatal period with signs of cardiopulmonary insufficiency. A combination of clinical, magnetic resonance imaging, and histological data indicated that lungs of Tpst double knockouts fail to expand at birth resulting in acute pulmonary hypertension, right-to-left shunting, and death by asphyxia in the early postnatal period. Some double knockouts survive the postnatal period, but fail to thrive and display delayed growth that is due in part to hypothyroidism. In addition, we find that Tpst2−/− mice have primary hypothyroidism, but that Tpst1−/− mice are euthyroid. This suggests that a protein(s) required for thyroid hormone production is sulfated and cannot be sulfated in the absence of TPST-2. Thus, Tpst1 and Tpst2 are the only Tpst genes in mice, tyrosine sulfation is required for normal pulmonary function at birth, and TPST-2 is required for normal thyroid gland function.

show abstract

Section: Discussionmentioning

confidence: 99%

Early postnatal pulmonary failure and primary hypothyroidism in mice with combined TPST-1 and TPST-2 deficiency

Westmuckett

Hoffhines

Borghei

et al. 2008

General and Comparative Endocrinology

View full text Add to dashboard Cite

show abstract

“…Eventually, proteolysis occurs with the release of T 4 and T 3 for secretion into the circulation while any residual iodine is recycled (177). Sulfonation plays an intimate role in thyroid physiology: it is important for both synthesis (178) and metabolism of thyroid hormones (179). In addition, TSH is subject to posttranslational modification by sulfonation (180,181).…”

Section: A Generalmentioning

confidence: 99%

“…The sulfate group could act to modify the electronic environment of the aromatic ring of tyrosine whereby it becomes more reactive for iodination and coupling; the sulfate group could be a recognition signal for thyroid peroxidase or the iodotyrosine donor (189). In a recent study (178), thyroid hormone synthesis was found to correlate with the sulfotyrosine content of thyroglobulin. Interestingly, a consensus sequence (Asp/Glu-Tyr) is similarly involved in thyroid hormone synthesis (190) and the sulfonation of tyrosine (191).…”

Section: B Sulfonation Of Thyroglobulinmentioning

confidence: 99%

“…Interestingly, a consensus sequence (Asp/Glu-Tyr) is similarly involved in thyroid hormone synthesis (190) and the sulfonation of tyrosine (191). Based on this observation, it has been proposed that thyroglobulin sulfotyrosines may act either as a signal for iodination or the coupling reaction (the latter is thought to be the more likely possibility) by inducing an interaction between thyroid peroxidase and thyroglobulin (178). Understanding the exact details of this complex system is a work in progress.…”

Section: B Sulfonation Of Thyroglobulinmentioning

confidence: 99%

See 1 more Smart Citation

Sulfonation and Molecular Action

2002

View full text Add to dashboard Cite

The sulfonation of endogenous molecules is a pervasive biological phenomenon that is not always easily understood, and although it is increasingly recognized as a function of fundamental importance, there remain areas in which significant cognizance is still lacking or at most minimal. This is particularly true in the field of endocrinology, in which the sulfoconjugation of hormones is a widespread occurrence that is only partially, if at all, appreciated. In the realm of steroid/sterol sulfoconjugation, the discovery of a novel gene that utilizes an alternative exon 1 to encode for two sulfotransferase isoforms, one of which sulfonates cholesterol and the other pregnenolone, has been an important advance. This is significant because cholesterol sulfate plays a crucial role in physiological systems such as keratinocyte differentiation and development of the skin barrier, and pregnenolone sulfate is now acknowledged as an important neurosteroid. The sulfonation of thyroglobulin and thyroid hormones has been extensively investigated and, although this transformation is better understood, there remain areas of incomplete comprehension. The sulfonation of catecholamines is a prevalent modification that has been extensively studied but, unfortunately, remains poorly understood. The sulfonation of pituitary glycoprotein hormones, especially LH and TSH, does not affect binding to their cognate receptors; however, sulfonation does play an important role in their plasma clearance, which indirectly has a significant effect on biological activity. On the other hand, the sulfonation of distinct neuroendocrine peptides does have a profound influence on receptor binding and, thus, a direct effect on biological activity. The sulfonation of specific extracellular structures plays an essential role in the binding and signaling of a large family of extracellular growth factors. In summary, sulfonation is a ubiquitous posttranslational modification of hormones and extracellular components that can lead to dramatic structural changes in affected molecules, the biological significance of which is now beginning to be appreciated.

show abstract

“…The biological role of tyrosine sulfation has been unclear, but recent studies have shown its functional importance in leukocyte adhesion (13)(14)(15)(16), hormone synthesis (17)(18)(19), chemokine receptor signaling (20 -26), and hemostasis (27)(28)(29)(30)(31)(32)(33).…”

mentioning

confidence: 99%

Identification of Tyrosine Sulfation in Extracellular Leucine-rich Repeat Proteins Using Mass Spectrometry

Önnerfjord

Heathfield

Heinegård

2004

Journal of Biological Chemistry

128

121

View full text Add to dashboard Cite

Multiple and variable tyrosine sulfation in extracellular class II leucine-rich repeat proteins/proteoglycans were characterized by mass spectrometry. The sulfogroup on tyrosine is labile and is released from peptides under normal mass spectrometric conditions. Thus, special approaches must be considered in order to identify this modification. By using a combination of mass spectrometry studies operating in negative and positive ion mode, tyrosine sulfation could be identified. In positive mode, the peptides normally appeared non-sulfated, whereas in negative mode a mixture of sulfated and non-sulfated species was observed. A combination of peptides released by different proteinases was used to obtain details on the locations of sulfate groups. Multiple tyrosine sulfates were observed in the N-terminal region of fibromodulin (up to 9 sites), osteoadherin (up to 6 sites), and lumican (2 sites). Osteoadherin contains two additional sulfated tyrosine residues close to its C terminus. We also identified an error in the published sequence of bovine fibromodulin, resulting in the replacement of Thr 37 by Tyr 37 -Gly 38 , thus increasing its homology with its human counterpart.Tyrosine sulfation is a post-translational modification found on many secreted and membrane-bound proteins. As much as 1% of all tyrosine residues of the total protein in an organism can be sulfated, making this the most common post-translational modification of this residue (1). A number of proteins have been reported to contain sulfated tyrosines (2). Sulfation is suggested to occur at tyrosines located in close proximity to acidic residues (3). The existence of two different tyrosylprotein sulfotransferases, TPST-1 1 and TPST-2, might explain the diversity of sequences that are sulfated. Each enzyme may have a different substrate specificity and act on a different subset of target proteins. Tyrosine sulfation of chemokine receptor CCR-5 by TPST-1 and TPST-2 follows a discrete pattern and temporal sequence (4). The N terminus contains the sulfation sites with 0 -4 sulfogroups present. TPST-1 null mice (5) appeared healthy but had a ϳ5% lower average body weight than wild type animals. In addition, although the fertility of (Ϫ/Ϫ) males and females is normal, they have significantly smaller litters because of fetal death between 8.5 and 15.5 days postcoitum.Regulation of tyrosine sulfation in vivo by enzymatic sulfate removal is still largely unknown. However, human arylsulfatase A and B reside in the lysosome where they are thought to participate in the degradation of tyrosine sulfated proteins (6). In contrast, arylsulfatase E is found in the Golgi compartment (7). Mutations in this gene cause chondrodysplasia punctata, a congenital disorder characterized by abnormalities in cartilage and bone development (7-12).The biological role of tyrosine sulfation has been unclear, but recent studies have shown its functional importance in leukocyte adhesion (13-16), hormone synthesis (17-19), chemokine receptor signaling (20 -26), and hemostasis (27-33)....

show abstract

Sulfated Tyrosines of Thyroglobulin Are Involved in Thyroid Hormone Synthesis

Cited by 18 publications

References 22 publications

Early postnatal pulmonary failure and primary hypothyroidism in mice with combined TPST-1 and TPST-2 deficiency

Early postnatal pulmonary failure and primary hypothyroidism in mice with combined TPST-1 and TPST-2 deficiency

Sulfonation and Molecular Action

Identification of Tyrosine Sulfation in Extracellular Leucine-rich Repeat Proteins Using Mass Spectrometry

Contact Info

Product

Resources

About