QSulf1, a heparan sulfate 6-
            <i>O</i>
            -endosulfatase, inhibits fibroblast growth factor signaling in mesoderm induction and angiogenesis

Wang, Shouwen; Ai, Xingbin; Freeman, Stephen; Pownall, Mary Elizabeth; Lu, Qi; Kessler, Daniel S.; Emerson, Charles P.

doi:10.1073/pnas.0401028101

Cited by 184 publications

(167 citation statements)

References 43 publications

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“…It has already been reported that de-sulfation of HSPG accounts for altered function. For example, avian QSULF1, a family member of Sulf2, inhibited angiogenesis in vitro [33]. Analogously, desulfation triggered by insulin via Sulf2 may induce functional changes in adipocytes.…”

Section: Discussionmentioning

confidence: 99%

Insulin modulates the secretion of proteins from mature 3T3-L1 adipocytes: a role for transcriptional regulation of processing

Wang

Keijer²,

Bunschoten³

et al. 2006

Diabetologia

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Aims/hypothesis Under conditions of insulin resistance and type 2 diabetes, fat cells are subjected to increased levels of insulin, which may have a major impact on the secretion of adipokines. Materials and methods Using transcriptomics and proteomics, we investigated how insulin affects the transcription and protein secretion profile of mature 3T3-L1 adipocytes. Results We found that insulin has a significant impact on protein secretion of 3T3-L1 adipocytes. However, transcription is not the major regulation point for these secreted proteins. For extracellular matrix components, our data suggest that the mRNA level of processing enzymes, but not of target proteins, is the regulating point at which insulin stimulates secretion and function of the relevant proteins. Among these enzymes, we report a novel finding, namely that sulfatase 2 gene is regulated by insulin, which may induce a functional change in cultured adipocytes. Conclusions/interpretation We propose that enhancement of protein processing and secretion rather than transcription of the secreted protein genes is part of the strategic role of insulin in the induction of cellular responses.

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Section: Discussionmentioning

confidence: 99%

Insulin modulates the secretion of proteins from mature 3T3-L1 adipocytes: a role for transcriptional regulation of processing

Wang

Keijer²,

Bunschoten³

et al. 2006

Diabetologia

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“…Specific sulfate groups (6S) have been shown to be dispensable for FGF2-HS binding, but critical for FGF/ FGFR2 signalling (Ishihara et al, 1995), and therefore removal of the 6-O-sulfate group disrupts FGF signalling (Wang et al, 2004). Similarly, VEGF binding and activity requires moderately 6-O sulfated HS (Ashikari-Hada et al, 2005;Robinson et al, 2006) and treatment of heparin with human SULF2 abolishes its binding to VEGF (Uchimura et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Dynamic expression patterns of 6‐O endosulfatases during zebrafish development suggest a subfunctionalisation event for sulf2

Gorsi

Whelan

2010

Developmental Dynamics

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The 6-O-endosulfatase enzymes (Sulfs) edit the final sulfation pattern and function of heparan sulfate (HS) by removal of 6-O-sulfate groups from the chain. To date, two mammalian sulf genes have been identified that regulate many signalling pathways during embryonic development. In zebrafish a sulf1 ortholog and duplicate copies of the mammalian sulf2 gene, sulf2a and sulf2, have been identified, which contain conserved motifs characteristic of vertebrate sulf genes. Zebrafish sulf1 and sulf2a are broadly expressed in the central nervous system (CNS) and non-neuronal tissue including heart, somite boundaries, olfactory system, and otic vesicle, whereas sulf2 expression is almost entirely restricted to the CNS. The duplicate copies of sulf2 have distinct expression patterns, which together mirror that of mouse sulf2, suggesting duplication in the teleost lineage has been followed by subfunctionalisation, whereby both genes need to be preserved by selection to ensure the ancestral gene's expression profile and function is maintained. Developmental Dynamics 239:3312-3323,

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“…HS 6-O-endosulfatases remove sulfate groups from specific positions along the HS chain. 6-O-sulfatase activity inhibits FGF signaling but has an opposing effect on WNT signaling Wang et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Systemic inactivation of Hs6st1 in mice is associated with late postnatal mortality without major defects in organogenesis

Izvolsky

Lü

Martin

et al. 2008

Genesis

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Summary: Heparan sulfate (HS) proteoglycans modulate the biological activity of a number of growth factors in development, homeostasis, and cancer. Specific modifications of HS chains by HS biosynthetic enzymes have been implicated in growth factor signaling in multiple aspects of organogenesis. Although the role of HS 6-O-sulfotransferases has been described in processes such as trachea formation in Drosophila and vasculogenesis in zebrafish, little is known about how HS 6-O-sulfotransferases (Hs6st1-3 in mice) influence mouse development. To address this issue, we generated a conditionally mutant Hs6st1 mouse line and then generated mice with systemic inactivation of Hs6st1. Hs6st1-null pups were viable and grossly normal at birth. The lack of obvious abnormalities in lung, liver, and kidney, which express high levels of Hs6st1 during development, suggests that at least during embryonic life, the loss of Hs6st1 function may be compensated for by mechanisms involving other HS modifying enzymes. During early adulthood, however, Hs6st1-null mice failed to thrive and exhibited growth retardation, body weight loss, enlargement of airspaces in the lung and, in some cases, lethality. Our results suggest a potentially critical role for HS 6-O sulfation by Hs6st1 in postnatal processes. genesis 46:8-18,

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QSulf1, a heparan sulfate 6- O -endosulfatase, inhibits fibroblast growth factor signaling in mesoderm induction and angiogenesis

Cited by 184 publications

References 43 publications

Insulin modulates the secretion of proteins from mature 3T3-L1 adipocytes: a role for transcriptional regulation of processing

Insulin modulates the secretion of proteins from mature 3T3-L1 adipocytes: a role for transcriptional regulation of processing

Dynamic expression patterns of 6‐O endosulfatases during zebrafish development suggest a subfunctionalisation event for sulf2

Systemic inactivation of Hs6st1 in mice is associated with late postnatal mortality without major defects in organogenesis

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