期刊
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
卷 1790, 期 10, 页码 1049-1058出版社
ELSEVIER
DOI: 10.1016/j.bbagen.2009.02.005
关键词
Klotho; FGF23; Phosphate; Vitamin D; Sialidase; TRPV5
资金
- NATIONAL INSTITUTE ON AGING [R01AG025326, R01AG019712] Funding Source: NIH RePORTER
- NIA NIH HHS [R01 AG025326-05, R01 AG019712, R01 AG025326, R01 AG019712-07] Funding Source: Medline
The klotho gene encodes a single-pass transmembrane protein that forms a complex with multiple fibroblast growth factor (FGF) receptors and functions as an obligatory co-receptor for FGF23. a bone-derived hormone that induces negative phosphate balance. Defects in either Klotho or Fgf23 gene expression cause not only phosphate retention but also a premature-aging syndrome in mice, unveiling a potential link between phosphate metabolism and aging. In addition, the extracellular domain of Klotho protein is clipped on the cell surface and secreted into blood stream, potentially functioning as an endocrine factor. The secreted Klotho protein has a putative sialidase activity that modifies glycans on the cell surface. which may explain the ability of secreted Klotho protein to regulate activity of multiple ion channels and growth factors including insulin, IGF-1, and Writ Secreted Klotho protein also protects cells and tissues from oxidative stress through a mechanism yet to be identified. Thus, the transmembrane and secreted forms of Klotho protein have distinct functions, which may collectively affect aging processes in mammals. (C) 2009 Elsevier B.V. All rights reserved.
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