Reactome | KAL1 binds HS

KAL1 binds HS

Stable Identifier

R-HSA-5654515

Type

Reaction [binding]

Species

Homo sapiens

Compartment

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 ligand binding and activation (Homo sapiens)
        
        KAL1 binds HS (Homo sapiens)

General

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KAL1 is an extracellular matrix-associated protein that modulates signaling by FGFR1c. Mutations in the KAL1 gene are associated with Kallmann syndrome, a genetic disorder characterized by olfactory bulb dysgenesis and hypogonadotrophic hypogonadism (Dode et al, 2003; Pitteloud et al, 2006; reviewed in Yu and Bouloux, 2010). KAL1 has been shown to interact with both FGFR1c and with heparan sulfate, with opposing effects on downstream signaling. Preformation of an FGFR1c:KAL1 complex inhibits the association of FGF ligand with the complex and subsequent receptor dimerization and in this way negatively regulates FGFR1c ligand-dependent signaling. In contrast, preformation of a KAL1:heparan sulfate complex promotes stable FGF ligand:receptor interaction thereby enhancing FGFR1c signal transduction (Hu et al, 2009; Hu et al, 2004; Soussi-Yanicostas et al, 1998).

Literature References

PubMed ID	Title	Journal	Year
19696444	Novel mechanisms of fibroblast growth factor receptor 1 regulation by extracellular matrix protein anosmin-1 Cadman, S, Kim, SH, Hohenester, E, Travers, P, Guimond, SE, Turnbull, JE, Hu, Y, Bouloux, PM	J. Biol. Chem.	2009
20117945	Novel insights in FGFR1 regulation: lessons from Kallmann syndrome Hu, Y, Bouloux, PM	Trends Endocrinol. Metab.	2010
15324302	Cross-talk of anosmin-1, the protein implicated in X-linked Kallmann's syndrome, with heparan sulphate and urokinase-type plasminogen activator Kim, SH, Bouloux, PM, González-Martínez, D, Hu, Y	Biochem. J.	2004
12627230	Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome Petit, C, Soussi-Yanicostas, N, Hardelin, JP, Goulet-Salmon, B, Delemarre-van de Waal, H, Delmaghani, S, Delpech, M, Levilliers, J, Dupont, JM, Le Tessier, D, Dodé, C, Kottler, ML, Le Dû, N, Saura, R, Amalfitano, A, Bachelot, Y, Speleman, F, Vermeulen, S, Cruaud, C, Baverel, F, Pêcheux, C, Richard, O, Sanchez-Franco, F, Carel, JC, De Paepe, A, Coimbra, RS, Compain-Nouaille, S, Young, J, Bouchard, P, Cabrol, S	Nat. Genet.	2003
16764984	Mutations in fibroblast growth factor receptor 1 cause Kallmann syndrome with a wide spectrum of reproductive phenotypes Dwyer, AA, Acierno, JS, Seminara, S, Fliers, E, Quinton, R, Ma, J, Meysing, A, Pitteloud, N, Crowley, WF, Plummer, L, Hayes, F, Boepple, P, Mohammadi, M, Hughes, VA, Bouloux, P	Mol. Cell. Endocrinol.	2006
9730987	Anosmin-1 underlying the X chromosome-linked Kallmann syndrome is an adhesion molecule that can modulate neurite growth in a cell-type specific manner Petit, C, Rougon, G, Soussi-Yanicostas, N, Hardelin, JP, Faivre-Sarrailh, C, Levilliers, J	J. Cell. Sci.	1998