Nuclear fibroblast growth factor-2 interacts specifically with splicing factor SF3a66

2004 ◽  
Vol 385 (12) ◽  
pp. 1203-1208 ◽  
Author(s):  
Susanne Gringel ◽  
Jeroen van Bergeijk ◽  
Kirsten Haastert ◽  
Claudia Grothe ◽  
Peter Claus
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Splicing Factor ◽  
Fibroblast Growth Factor 2 ◽  
Interacting Proteins ◽  
Fibroblast Growth ◽  
Extracellular Signaling ◽  
C Terminus ◽  
Assembly Factor ◽  
Smn Protein

Abstract Fibroblast growth factor 2 (FGF-2) has a dual role as a classical extracellular signaling protein and as an intracellular factor. Isoforms of FGF-2, resulting from alternatively used start codons on one mRNA species, locate differentially to nuclear compartments. In this study we aimed to analyze functions of intracellular FGF-2 by identification of interacting proteins. We identified the 66-kDa subunit of splicing factor 3a (SF3a66) as a binding partner in a yeast two-hybrid screen and confirmed this interaction by pull-down assays. The splicing factor interacted with the 18-kDa (FGF-218) and with the 23-kDa (FGF-223) isoforms, indicating an interaction with a domain common to both isoforms. Moreover, FGF-2 interacted with the C-terminus of SF3a66, a sequence that has not previously been assigned a functional role. In a functional neurite outgrowth assay, SF3a66 enhanced neurite lengths similar to FGF-218. We have previously identified the spliceosomal assembly factor survival of motoneuron (SMN) protein as a protein interacting specifically with the FGF-223 isoform [Claus et al., J. Biol. Chem. 278 (2003), 479–485]. The identification of two FGF-2 interacting proteins from the same biochemical pathway suggests a novel intranuclear role of FGF-2.

Fibroblast growth factor 2 (FGF-2) is a novel substrate for arginine methylation by PRMT5

2009 ◽  
Vol 390 (1) ◽  
Author(s):  
Alexander-Francisco Bruns ◽  
Claudia Grothe ◽  
Peter Claus
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Arginine Methylation ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
Sm Proteins ◽  
Small Nuclear Ribonucleoprotein ◽  
Smn Protein ◽  
Nuclear Ribonucleoprotein

Abstract Fibroblast growth factor 2 (FGF-2) is expressed in isoforms of different molecular masses from one mRNA species by alternative start of translation. The higher molecular mass isoforms (FGF-221 and 23) contain an arginine-rich N-terminus organized in RG-motifs followed by the 18 kDa FGF-2 (FGF-218) core which is common to all isoforms. Both isoforms localize differentially to the nucleus. Here, we analyzed the nuclear localization of FGF-221. Surprisingly, the lack of one RG-motif in FGF-221 resulted in the nucleolar distribution characteristic of FGF-218. We have previously shown that 23 kDa FGF-2 (FGF-223) interacts specifically with the survival of motoneuron (SMN) protein, an assembly protein for small nuclear ribonucleoprotein particles. For this assembly, Sm-proteins methylated by protein arginine methyltransferase 5 (PRMT5) are required. In our study, we aimed to analyze whether FGF-223 is also a substrate for symmetrical methylation by PRMT5. We could confirm that both proteins exist in a common complex. Moreover, PRMT5 methylates FGF-223 in vitro, whereas mutated inactive PRMT5 does not. FGF-223 is therefore a new substrate of PRMT5. With regard to function, inhibition of methyltransferase activity in HEK293T cells leads to cytoplasmic enrichment of FGF-2, indicating the importance of arginine methylation for shuttling of FGF-223 to the nucleus.

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