title: Fibroblast growth factor-2(23) binds directly to the survival of motoneuron protein and is associated with small nuclear RNAs.
abstract: The SMN (survival of motoneuron) protein is mutated in patients with the neurodegenerative disease spinal muscular atrophy. We have shown previously that a high-molecular-mass isoform of FGF (fibroblast growth factor) 2 (FGF-2(23)) is in a complex with SMN [Claus, Doring, Gringel, Muller-Ostermeyer, Fuhlrott, Kraft and Grothe (2003) J. Biol. Chem. 278, 479-485]. FGF-2 is a neurotrophic factor for motoneurons, and is known not only as a classical extracellular growth factor, but also as a nuclear protein. In the present study, we demonstrate that SMN binds to the arginine-rich N-terminus of FGF-2(23). In turn, FGF-2(23) interacts with amino acid residues 1-90 of the human SMN protein. This sequence displays nucleic-acid-binding capacity and overlaps partially with known binding sites for Gemin2/SIP1 (SMN-interacting protein 1) and p53. Finally, as a functional consequence of FGF-2(23) binding to SMN, FGF-2(23) is in a complex with the small nuclear RNAs U2 and U4. Since SMN functions as an assembly factor for snRNPs (small nuclear ribonucleoprotein particles), these results suggest binding of FGF-2(23) to snRNPs.
authors.affiliation: Department of Neuroanatomy, Hannover Medical School, OE 4140, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. claus.peter@mh-hannover.de
authors.forename: Peter
authors.initials: P
authors.lastname: Claus
authors.forename: Alexander-Francisco
authors.initials: AF
authors.lastname: Bruns
authors.forename: Claudia
authors.initials: C
authors.lastname: Grothe
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001120:Arginine / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D009046:Motor Neurons; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012342:RNA, Small Nuclear / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D012260:Ribonucleases / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055532:SMN Complex Proteins; D012583:Schwann Cells; D055533:Survival of Motor Neuron 1 Protein
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D012342:RNA, Small Nuclear; D016601:RNA-Binding Proteins; D017411:Ribonucleoproteins, Small Nuclear; D055532:SMN Complex Proteins; C526473:Smn1 protein, rat; D055533:Survival of Motor Neuron 1 Protein; C405484:U2 small nuclear RNA; D016222:Fibroblast Growth Factor 2; D001120:Arginine; D012260:Ribonucleases