Meta-Biol

• Pathways

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).