Reactome | Autocatalytic phosphorylation of Klotho-bound FGFR1c

Autocatalytic phosphorylation of Klotho-bound FGFR1c

Stable Identifier

R-HSA-191062

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane, cytosol, extracellular region

ReviewStatus

5/5

Locations in the PathwayBrowser

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Signal Transduction (Homo sapiens)

- Signaling by Receptor Tyrosine Kinases (Homo sapiens)
  - Signaling by FGFR (Homo sapiens)
    - Signaling by FGFR1 (Homo sapiens)
      - FGFR1 ligand binding and activation (Homo sapiens)
        
        FGFR1c and Klotho ligand binding and activation (Homo sapiens)
        
        Autocatalytic phosphorylation of Klotho-bound FGFR1c (Homo sapiens)

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Autocatalytic phosphorylation of Klotho-bound FGFR1c

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Studies have mapped 8 tyrosine residues in the cytoplasmic domain of FGFR1 that are important for signaling. Autophosphorylation of residues 653 and 654, located in the activation loop of the kinase, is necessary to maintain the receptor in the active state. Phosphorylation of other tyrosine residues by the intrinsic protein tyrosine kinase activity of the activated receptor creates binding sites on its cytoplasmic tail for membrane bound docking proteins to gather intracellular signaling mediators.

Literature References

PubMed ID	Title	Journal	Year
8622701	Identification of six novel autophosphorylation sites on fibroblast growth factor receptor 1 and elucidation of their importance in receptor activation and signal transduction Mohammadi, M, Dikic, I, Sorokin, A, Burgess, WH, Jaye, M, Schlessinger, J	Mol Cell Biol	1996
16507368	Autophosphorylation of FGFR1 kinase is mediated by a sequential and precisely ordered reaction Furdui, CM, Lew, ED, Schlessinger, J, Anderson, KS	Mol Cell	2006
17086194	Klotho converts canonical FGF receptor into a specific receptor for FGF23 Fujita, T, Fukumoto, S, Hasegawa, H, Iijima, K, Okawa, K, Shimada, T, Urakawa, I, Yamazaki, Y, Yameshita, T	Nature	2006
1379698	Point mutation in FGF receptor eliminates phosphatidylinositol hydrolysis without affecting mitogenesis Mohammadi, M, Dionne, CA, Li, W, Li, N, Spivak, T, Honegger, AM, Jaye, M, Schlessinger, J	Nature	1992
11294897	Identification of tyrosine residues in constitutively activated fibroblast growth factor receptor 3 involved in mitogenesis, Stat activation, and phosphatidylinositol 3-kinase activation Hart, KC, Robertson, SC, Donoghue, DJ	Mol Biol Cell	2001