Fibroblast growth factor-2(23) binds directly to the survival of motoneuron protein and is associated with small nuclear RNAs.
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.
Claus
Peter
P
Department of Neuroanatomy, Hannover Medical School, OE 4140, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. claus.peter@mh-hannover.de
Bruns
Alexander-Francisco
AF
Grothe
Claudia
C
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
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