Fibroblast growth factor homologous factors are intracellular signaling proteins

Fibroblast growth factors (FGFs) mediate cell growth, differentiation, migr ation, and morphogenesis by binding to the extracellular domain of cell sur face receptors, triggering receptor tyrosine phosphorylation and signal tra nsduction [1-5]. FGF homologous factors (FHFs) were discovered within verte brate DNA sequence databases by virtue of their sequence similarity to FGFs [3, 6, 7], but the mechanism of FHF action has not been reported. We show here that FHF-1 is associated with the MAP kinase (MAPK) scaffold protein I slet-Brain-2 (IB2) [8] in the brain and in specific cell lines. FHF/IB2 int eraction is highly specific, as FHFs do not bind to the related scaffold pr otein IB1(JIP-1b) [9, 10], nor can FGF-1 bind to IB2. We further show that FHFs enable IB2 to recruit a specific MAPK in transfected cells, and our da ta suggest that the scaffolds IB1 and IB2 have different MAPK specificities . Hence, FHFs are intracellular components of a tissue-specific protein kin ase signaling module.