Fibroblast growth factor homologous factors: evolution, structure, and function.
Fibroblast growth factor homologous factors (FHFs) bear strong sequence and structural similarity to fibroblast growth factors (FGFs). However, the biochemical and functional properties of FHFs are largely, if not totally, unrelated to those of FGFs. Whereas FGFs function through binding to the extracellular domains of FGF receptors (FGFRs), FHFs bind to intracellular domains of voltage-gated sodium channels (VGSCs) and to a neuronal MAP kinase scaffold protein, islet-brain-2 (IB2). These findings demonstrate the remarkable functional adaptability during evolution of the FGF gene family. FHF gene mutations in mice result in a range of neurological abnormalities, and at least one of these anomalies, cerebellar ataxia, is linked to FHF mutations in humans. This article reviews the sequences and structure of FHFs, along with our still limited understanding of FHF function.
Goldfarb
Mitchell
M
Department of Biological Sciences, Hunter College of City University, New York, NY 10021, USA.
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000818:Animals; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D051379:Mice; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology*; D017468:Receptors, Fibroblast Growth Factor / Q000187:drug effects; D015398:Signal Transduction / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; C408376:MAPK8IP2 protein, human; D024642:Potassium Channels, Voltage-Gated; D017468:Receptors, Fibroblast Growth Factor; C108111:fibroblast growth factor 13; D005346:Fibroblast Growth Factors