Differential Enzymatic Characteristics and Tissue-Specific Expression of Human TPST-1 and TPST-2

Mishiro, Emi; Sakakibara, Yoichi; Liu, Ming‐Cheh; Suiko, Masahito

doi:10.1093/jb/mvj206

Cited by 49 publications

(60 citation statements)

References 40 publications

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“…This means that grt mice develop hypothyroidism and growth retardation because they are unable to fully respond to TSH (Sasaki et al 2007). It has been reported that TPST2 is ubiquitously expressed (Mishiro et al 2006). However, there has been no report concerning the expression of TPST2 in mouse pancreatic islets.…”

Section: Tpst2mentioning

confidence: 99%

Impaired insulin secretion from the pancreatic islets of hypothyroidal growth-retarded mice

Taguchi¹,

Tasaki²,

Terakado³

et al. 2010

Journal of Endocrinology

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The growth-retarded (grt) mouse shows thyroid dysfunctionrelated hyporesponsiveness to TSH. Thyroid hormone is a critical regulator of metabolism in many cells; thus, derangement of thyroid function affects many organs and systems. Experiments were conducted focusing on the function of the pancreatic islets in grt mice. We showed occurrence of a fasting hyperglycemia and a decreased plasma insulin level response to a glucose load in grt mice, despite normal insulin molecules being stored in secretory granules of pancreatic islets. We also demonstrated a reduction of insulin secretion in response to glucose administration from islets of grt mice in vitro, while the insulin release in response to KCl stimulation was comparable to that in normal mice, indicating that the isolated islets from grt mice have normal ATPsensitive K C channels and postchannel activity. The mRNA expression levels of glucose transporter 2 and glucokinase in the islets of grt mice were similar to those in normal mice. Triiodothyronine administration to grt mice improved insulin secretion very slightly. On the other hand, mRNA for tyrosylprotein sulfotransferase 2 (Tpst2) was found to be expressed in the pancreatic islets of grt mice. Considering that Tpst2 is the responsible gene of grt mice, mutation of which is associated with a poor function of TSH receptor, the findings raise a possibility of involvement of factors including Tpst2 in the insulin hyposecretion in grt mice.

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Section: Tpst2mentioning

confidence: 99%

Impaired insulin secretion from the pancreatic islets of hypothyroidal growth-retarded mice

Taguchi¹,

Tasaki²,

Terakado³

et al. 2010

Journal of Endocrinology

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“…The sulfate transfer is catalyzed by two independent tyrosylprotein sulfotransferases (TPST, 3′-phosphoadenylyl-sulfate:protein-tyrosine O -sulfotransferase, EC 2.8.2.20) (Lee and Huttner, 1983;Moore, 2003). The two TPST enzymes differ in their acidic pH optima, degree of stimulation by Mn 2+ and Mg 2+ (Mishiro et al, 2006) and have differential substrate affinities. Compared with TPST-2, TPST-1 exhibits significantly lower K m and V max for the majority of the substrates tested (Mishiro et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…The two TPST enzymes differ in their acidic pH optima, degree of stimulation by Mn 2+ and Mg 2+ (Mishiro et al, 2006) and have differential substrate affinities. Compared with TPST-2, TPST-1 exhibits significantly lower K m and V max for the majority of the substrates tested (Mishiro et al, 2006). This is corroborated by the finding that in comparison to TPST-1, TPST-2 has a high degree of substrate preference towards the thyroid stimulating hormone receptor (Sasaki et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…This is corroborated by the finding that in comparison to TPST-1, TPST-2 has a high degree of substrate preference towards the thyroid stimulating hormone receptor (Sasaki et al, 2007). Furthermore, studies on the expression of TPST-1 and TPST-2 demonstrated significant variations in the levels of expression among different tissues, suggesting distinct physiological functions for TPST-1 and TPST-2 (Mishiro et al, 2006;Ouyang, Lane et al, 1998;Ouyang and Moore, 1998;Beisswanger et al, 1998;Nishimura and Naito, 2007). …”

Section: Introductionmentioning

confidence: 99%

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Protein tyrosine-O-sulfation in the retina

Kanan

Hoffhines

Rauhauser

et al. 2009

Experimental Eye Research

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Tyrosine-O-sulfation, a post-translational modification, is catalyzed by two independent tyrosylprotein sulfotransferases (TPSTs). As an initial step towards understanding the role of TPSTs in retinal function, this study was undertaken to determine the extent to which tyrosine-O-sulfation of proteins is utilized in the retina. A previously characterized anti-sulfotyrosine antibody was used to determine the presence and localization of tyrosine-O-sulfated proteins (TOSPs) in the retina. Using Western blot, RT-PCR and immunohistochemical analyses, we detected TOSPs in the retinas from diverse species, including frog, fish, mouse and human. Some of the variability in the observed sizes of retinal TOSPs in the mouse, at least, may result from differential patterns of glycosylation; however, there seem to be species-specific sulfated retinal proteins as well. TOSPs were detected in most of the retinal layers as well as in the retinal pigment epithelium from human and mouse. Several retinal TOSPs were detected in the inter-photoreceptor matrix, which is consistent with the secreted nature of some sulfated proteins. Transcripts for both TPST-1 and -2 were expressed in both the human and mouse retinas. These data show that retinal protein tyrosine-O-sulfation is highly conserved which suggest a functional significance of these proteins to retinal function and structure.

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“…In cell culture experiments, both TPST enzymes are capable of trypsinogen sulfation [20]. In the human pancreas, TPST2 is expressed at levels 50-fold higher than TPST1, indicating that physiological trypsinogen sulfation is mediated by TPST2 [18,21,22]. Notably, TPST2 expression is approximately 10-fold higher in the pancreas than in other human tissues.…”

Section: Introductionmentioning

confidence: 99%

Sequence Analysis of the Human Tyrosylprotein Sulfotransferase-2 Gene in Subjects with Chronic Pancreatitis

et al. 2010

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Background/Aims: Human trypsinogens are post-translationally sulfated on Tyr154 by the Golgi resident enzyme tyrosylprotein sulfotransferase-2 (TPST2). Tyrosine sulfation stimulates the autoactivation of human cationic trypsinogen. Because increased trypsinogen autoactivation has been implicated as a pathogenic mechanism in chronic pancreatitis, we hypothesized that genetic variants of TPST2 might alter the risk for the disease. Methods: We sequenced the 4 protein-coding exons and the adjacent intronic sequences of TPST2 in 151 subjects with chronic pancreatitis and in 169 healthy controls. The functional effect of TPST2 variants on trypsinogen sulfation was analyzed in transfected HEK 293T cells. Results: We detected 10 common polymorphic variants, including 6 synonymous variants and 4 intronic variants, with similar frequencies in patients and controls. None of the 8 common haplotypes reconstructed from the frequent variants showed an association with chronic pancreatitis. In addition, we identified 5 rare TPST2 variants, which included 3 synonymous alterations, the c.458G>A (p.R153H) nonsynonymous variant and the c.-9C>T variant in the 5′ untranslated region. The p.R153H variant was found in a family with hereditary pancreatitis; however, it did not segregate with the disease. In functional assays, both the p.R153H and c.-9C>T TPST2 variants catalyzed trypsinogen sulfation as well as wild-type TPST2. Conclusion: Genetic variants of human TPST2 exert no influence on the risk of chronic pancreatitis.

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Differential Enzymatic Characteristics and Tissue-Specific Expression of Human TPST-1 and TPST-2

Cited by 49 publications

References 40 publications

Impaired insulin secretion from the pancreatic islets of hypothyroidal growth-retarded mice

Impaired insulin secretion from the pancreatic islets of hypothyroidal growth-retarded mice

Protein tyrosine-O-sulfation in the retina

Sequence Analysis of the Human Tyrosylprotein Sulfotransferase-2 Gene in Subjects with Chronic Pancreatitis

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