Polypeptide GalNAc-transferase T3 and familial tumoral calcinosis - Secretion of fibroblast growth factor 23 requires O-glycosylation
Polypeptide GalNAc-transferase T3 and familial tumoral calcinosis - Secretion of fibroblast growth factor 23 requires O-glycosylation
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DOI：
10.1074/jbc.m602469200
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发表时间：
2006-07-07
影响因子：
4.8
通讯作者：
Clausen, Henrik
中科院分区：
文献类型：
--
作者：
Kato, Kentaro;Jeanneau, Charlotte;Clausen, Henrik
编码糖基转移酶多肽GalNAc-T3的基因突变参与了O-糖基化的启动，最近被发现是罕见的常染色体隐性代谢紊乱家族性肿瘤钙质沉着症(OMIM 211900)的原因之一。家族性肿瘤钙质沉着症与高磷血症和大量异位钙化有关。在这里，我们证明了磷酸尿因子成纤维细胞生长因子23(FGF23)的分泌需要O-糖基化，而GalNAc-T3选择性地在枯草杆菌蛋白原蛋白转换酶识别序列基序中指导O-糖基化，从而阻止FGF23的加工。这项研究提出了一种新的FGF23翻译后调控模型，涉及竞争O-糖基化和蛋白酶加工以产生完整的FGF23。
Mutations in the gene encoding the glycosyltransferase polypeptide GalNAc-T3, which is involved in initiation of O-glycosylation, were recently identified as a cause of the rare autosomal recessive metabolic disorder familial tumoral calcinosis (OMIM 211900). Familial tumoral calcinosis is associated with hyperphosphatemia and massive ectopic calcifications. Here, we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 (FGF23) requires O-glycosylation, and that GalNAc-T3 selectively directs O-glycosylation in a subtilisin-like proprotein convertase recognition sequence motif, which blocks processing of FGF23. The study suggests a novel posttranslational regulatory model of FGF23 involving competing O-glycosylation and protease processing to produce intact FGF23.