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PMID:16436388

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Citation

Kurosu, H, Ogawa, Y, Miyoshi, M, Yamamoto, M, Nandi, A, Rosenblatt, KP, Baum, MG, Schiavi, S, Hu, MC, Moe, OW and Kuro-o, M (2006) Regulation of fibroblast growth factor-23 signaling by klotho. J. Biol. Chem. 281:6120-3

Abstract

The aging suppressor gene Klotho encodes a single-pass transmembrane protein. Klotho-deficient mice exhibit a variety of aging-like phenotypes, many of which are similar to those observed in fibroblast growth factor-23 (FGF23)-deficient mice. To test the possibility that Klotho and FGF23 may function in a common signal transduction pathway(s), we investigated whether Klotho is involved in FGF signaling. Here we show that Klotho protein directly binds to multiple FGF receptors (FGFRs). The Klotho-FGFR complex binds to FGF23 with higher affinity than FGFR or Klotho alone. In addition, Klotho significantly enhanced the ability of FGF23 to induce phosphorylation of FGF receptor substrate and ERK in various types of cells. Thus, Klotho functions as a cofactor essential for activation of FGF signaling by FGF23.

Links

PubMed PMC2637204 Online version:10.1074/jbc.C500457200

Keywords

Animals; Cell Line; Fibroblast Growth Factors/deficiency; Fibroblast Growth Factors/genetics; Fibroblast Growth Factors/metabolism; Glucuronidase/genetics; Glucuronidase/physiology; HeLa Cells; Humans; Mice; Mice, Knockout; PC12 Cells; Rats; Receptors, Fibroblast Growth Factor/metabolism; Signal Transduction/genetics; Signal Transduction/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:KLOT

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q03142

F

Seeded From UniProt

complete

MOUSE:KLOT

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P21803

F

Seeded From UniProt

complete

MOUSE:KLOT

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

MGI:MGI:95524

F

Seeded From UniProt

complete

MOUSE:KLOT

acts_upstream_of_or_within

GO:0090080: positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1891427

P

Seeded From UniProt

complete

MOUSE:FGFR2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:O35082

F

Seeded From UniProt

complete

MOUSE:FGFR4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:O35082

F

Seeded From UniProt

complete

MOUSE:FGFR3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:O35082

F

Seeded From UniProt

complete

MOUSE:FGF23

acts_upstream_of_or_within

GO:0008543: fibroblast growth factor receptor signaling pathway

ECO:0000353: physical interaction evidence used in manual assertion

PR:O35082
PR:P16092

P

Seeded From UniProt

complete

MOUSE:FGF23

enables

GO:0005104: fibroblast growth factor receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:O35082
PR:P16092

F

Seeded From UniProt

complete

MOUSE:FGF23

acts_upstream_of_or_within

GO:0090080: positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1101771

P

Seeded From UniProt

complete

MOUSE:KLOT

acts_upstream_of_or_within

GO:0090080: positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1890427

P

Seeded From UniProt

complete


See also

References

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