KAL1 binds HS

Stable Identifier
R-HSA-5654515
Type
Reaction [binding]
Species
Homo sapiens
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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
20117945 Novel insights in FGFR1 regulation: lessons from Kallmann syndrome

Hu, Y, Bouloux, PM

Trends Endocrinol. Metab. 2010
19696444 Novel mechanisms of fibroblast growth factor receptor 1 regulation by extracellular matrix protein anosmin-1

Hu, Y, Guimond, SE, Travers, P, Cadman, S, Hohenester, E, Turnbull, JE, Kim, SH, Bouloux, PM

J. Biol. Chem. 2009
15324302 Cross-talk of anosmin-1, the protein implicated in X-linked Kallmann's syndrome, with heparan sulphate and urokinase-type plasminogen activator

Hu, Y, González-Martínez, D, Kim, SH, Bouloux, PM

Biochem. J. 2004
12627230 Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome

Dodé, C, Levilliers, J, Dupont, JM, De Paepe, A, Le Dû, N, Soussi-Yanicostas, N, Coimbra, RS, Delmaghani, S, Compain-Nouaille, S, Baverel, F, Pêcheux, C, Le Tessier, D, Cruaud, C, Delpech, M, Speleman, F, Vermeulen, S, Amalfitano, A, Bachelot, Y, Bouchard, P, Cabrol, S, Carel, JC, Delemarre-van de Waal, H, Goulet-Salmon, B, Kottler, ML, Richard, O, Sanchez-Franco, F, Saura, R, Young, J, Petit, C, Hardelin, JP

Nat. Genet. 2003
16764984 Mutations in fibroblast growth factor receptor 1 cause Kallmann syndrome with a wide spectrum of reproductive phenotypes

Pitteloud, N, Meysing, A, Quinton, R, Acierno, JS, Dwyer, AA, Plummer, L, Fliers, E, Boepple, P, Hayes, F, Seminara, S, Hughes, VA, Ma, J, Bouloux, P, Mohammadi, M, Crowley, WF

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

Soussi-Yanicostas, N, Faivre-Sarrailh, C, Hardelin, JP, Levilliers, J, Rougon, G, Petit, C

J. Cell. Sci. 1998
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