Fibroblast growth factor 2 (FGF-2) is an important modulator of cell growth and differentiation and a neurotrophic factor. FGF-2 occurs in isoforms, at a low molecular weight of 18,000 and at least two high molecular weight forms (21,000 and 23,000), representing alternative translation products from a single mRNA. In addition to its role as an extracellular ligand, FGF-2 localizes to the nuclei of cells. Here we show differential localization of the 18-and 23-kDa isoforms in the nuclei of rat Schwann cells. Whereas the 18-kDa isoform was found in the nucleoli, nucleoplasm, and Cajal bodies, the 23-kDa isoform localized in a punctuate pattern and associates with mitotic chromosomes suggesting different functional roles of the isoforms. Moreover, we show here that the 23-kDa FGF-2 isoform co-immunoprecipitates specifically with the survival of motor neuron protein (SMN). SMN is an assembly and recycling factor of the splicing machinery and locates to the cytoplasm, the nucleoplasm, and nuclear gems, where it co-localizes with 23-kDa FGF-2. Patients with spinal muscular atrophy suffer from fatal degeneration of motoneurons because of mutations and deletions of the gene for the SMN protein.A number of mitogenic growth factors, growth-regulatory proteins, and growth factor receptors have been reported to be localized in the cell nucleus and its substructures: e.g. plateletderived growth factor, fibroblast growth factor-1 (FGF-1), 1 FGF-2, and ciliary neurotrophic factor (1, 2). The data show that nuclear localization is a general phenomenon for some growth factors, suggesting nuclear functions independent of the function as extracellular factors.FGF-2 is a member of the FGF family, which has been shown to mediate a variety of biological processes during development and in the adult organism, including mitogenesis, angiogenesis, chemotaxis, mesoderm induction, and differentiation of various mesoderm-and neuroectoderm-derived cells. FGF-2 as an extracellular ligand is able to bind to high affinity tyrosine transmembrane receptors (FGF receptors, FGFR). FGF-2 has been shown to bind to all four known FGFR, however, with distinct affinities (3).FGF-2 exists in protein isoforms translated from a common messenger RNA by alternative use of AUG (18,000 isoform) and CUG (high molecular weight isoforms 21,000 and 23,000) start codons. The isoforms exert different biological effects when overexpressed in different cell types. Specific effects seen by the 23-kDa isoform but not the 18-kDa isoform after overexpression are reduced spreading of pancreatic cancer cells (4), the ability of NIH 3T3 cells to grow in low serum medium (5), increased radioresistance in HeLa cells (6), growing in serumfree medium of rat AR4 -2J cells (7), and differential effects on binucleation and nuclear morphology of neonatal rat cardiac myocytes (8). We have previously shown that in PC12 cells and rat immortalized Schwann cells, cell growth and morphology are altered after transfection with constructs coding for 18-and 23-kDa FGF-2, respectively (9, 1...

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