title: Fibroblast growth factor homologous factors are intracellular signaling proteins.
abstract: Fibroblast growth factors (FGFs) mediate cell growth, differentiation, migration, and morphogenesis by binding to the extracellular domain of cell surface receptors, triggering receptor tyrosine phosphorylation and signal transduction [1-5]. FGF homologous factors (FHFs) were discovered within vertebrate 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 Islet-Brain-2 (IB2) [8] in the brain and in specific cell lines. FHF/IB2 interaction is highly specific, as FHFs do not bind to the related scaffold protein 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 data suggest that the scaffolds IB1 and IB2 have different MAPK specificities. Hence, FHFs are intracellular components of a tissue-specific protein kinase signaling module.
authors.affiliation: Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: J
authors.initials: J
authors.lastname: Schoorlemmer
authors.forename: M
authors.initials: M
authors.lastname: Goldfarb
mesh_terms: D000818:Animals; D005346:Fibroblast Growth Factors / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction / Q000502:physiology*; D020798:Two-Hybrid System Techniques
chemical_list: D005346:Fibroblast Growth Factors; D020928:Mitogen-Activated Protein Kinases