Klotho converts canonical FGF receptor into a specific receptor for FGF23

  title={Klotho converts canonical FGF receptor into a specific receptor for FGF23},
  author={Itaru Urakawa and Yuji Yamazaki and Takashi Shimada and Kousuke Iijima and Hisashi Hasegawa and Katsuya Okawa and Toshiro Fujita and Seiji Fukumoto and Takeyoshi Yamashita},
FGF23 is a unique member of the fibroblast growth factor (FGF) family because it acts as a hormone that derives from bone and regulates kidney functions, whereas most other family members are thought to regulate various cell functions at a local level. The renotropic activity of circulating FGF23 indicates the possible presence of an FGF23-specific receptor in the kidney. Here we show that a previously undescribed receptor conversion by Klotho, a senescence-related molecule, generates the FGF23… 

Agonistic β-Klotho antibody mimics fibroblast growth factor 21 (FGF21) functions

A molecular model wherein the agonistic antibody 39F7 acts in a β-Klotho– and FGFR1c-dependent manner, mimicking FGF21 activity is proposed, offering promising therapeutic potential in the axis of FGF 21 signaling as an antibody therapy alternative to FGF23 analogs for treatment of metabolic diseases.

The Klotho gene family as a regulator of endocrine fibroblast growth factors

The Klotho gene family and the endocrine fibroblast growth factors

Purpose of reviewThis review summarizes recent progress in understanding of Klotho and βKlotho function in the regulation of tissue-specific metabolic activity of the endocrine fibroblast growth

αKlotho is a Non-Enzymatic Molecular Scaffold for FGF23 Hormone Signaling

The ageing suppressor α-klotho binds to the fibroblast growth factor receptor (FGFR). This commits FGFR to respond to FGF23, a key hormone in the regulation of mineral ion and vitamin D homeostasis.

FGF23 Actions on Target Tissues—With and Without Klotho

The signaling and cellular events that are caused by FGF23 in tissues lacking klotho are described, and FGF 23’s potential role as a hormone with widespread pathologic actions is discussed.

Pleiotropic Actions of FGF23

  • R. Erben
  • Biology, Medicine
    Toxicologic pathology
  • 2017
There is emerging evidence that FGF23 is a pleiotropic hormone, linking bone with several other organ systems, and may have important implications for the pathophysiology of chronic kidney disease.

Co-receptor Requirements for Fibroblast Growth Factor-19 Signaling*

The results suggest that a functional FGF19 receptor may consist of FGF receptor (FGFR) and heparan sulfate complexed with either αKlotho or βKlothso, which are related to each other and highly expressed in liver and fat.



Analysis of the biochemical mechanisms for the endocrine actions of fibroblast growth factor-23.

It is proposed that F GF23 signals through multiple FGFRs and that the unique endocrine actions of FGF23 involve escape from FGF 23-producing cells and circulation to the kidney, where highly sulfated GAGs most likely act as cofactors for FGF21 activity.

Fibroblast growth factors

A subset of the FGF family, expressed in adult tissue, is important for neuronal signal transduction in the central and peripheral nervous systems.

Fibroblast Growth Factor (FGF)-23 Inhibits Renal Phosphate Reabsorption by Activation of the Mitogen-activated Protein Kinase Pathway*

The present findings have revealed a novel MAPK-dependent mechanism of the regulation of phosphate uptake by FGF signaling, which was found to require heparin-like molecules for its inhibitory activity on phosphate uptake.

Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism.

Evidence is presented that FGF23 is a physiological regulator of serum phosphate and 1,25-dihydroxyvitamin D (1,25[OH]2D) by generating FGF 23-null mice, indicating that F GF23 is essential for normal phosphate and vitamin D metabolism.

FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting.

It is found that FGF-23 is produced by normal and FD osteoprogenitors and bone-forming cells in vivo and in vitro and may play an important role in the renal phosphate-wasting syndrome associated with FD/MAS.

Evolution of the Fgf and Fgfr gene families.

Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia

It is concluded that overproduction of F GF23 causes TIO, whereas mutations in the FGF23 gene result in autosomal dominant hypophosphatemic rickets possibly by preventing proteolytic cleavage and enhancing biological activity of FGF 23.

Klotho: a fundamental regulator of aging

Signal transduction by fibroblast growth factor receptor-4 (FGFR-4). Comparison with FGFR-1.

FGFR-4 induced only a barely detectable phosphorylation of the cellular serine/threonine kinase Raf-1 and a weaker tyrosyl phosphorylated of mitogen-activated protein kinases than FGFR-1, and stimulation of both receptors resulted in increased DNA synthesis.