Cloning of an intracellular protein that binds selectively to mitogenic acidic fibroblast growth factor

Abstract

In addition to its extracellular action, there is evidence that acidic fibroblast growth factor (aFGF) acts inside cells. To identify intracellular proteins interacting with aFGF, we screened a HeLa cell library in the yeast two-hybrid system using pLex-aFGF as a bait. A clone binding to aFGF, but not to the non-mitogenic mutant aFGF-K132E, was isolated and characterized. The insert contained an open reading frame corresponding to a novel protein of 42 kDa. The protein, termed aFGF intracellular binding protein (FIBP), is mainly hydrophilic and does not contain an N-terminal signal sequence. In vitro-translated FIBP bound specifically to a fusion protein of maltose-binding protein and aFGF. FIBP became post-translationally associated with microsomes added to the cell-free protein synthesizing system, and the membrane-associated protein bound aFGF with high efficiency. Immunoblots and fluorescence microscopy demonstrated that the protein is present in nuclei and, to a lesser extent, associated with mitochondria and other cytoplasmic membranes. The possibility is discussed that FIBP may be involved in the mitogenic action of aFGF.

Expression profiling reveals altered satellite cell numbers and glycolytic enzyme transcription in nemaline myopathy muscle

“…4A, Table 3). Furthermore, FIBP, a gene believed to promote mitogenesis and normally highly expressed in skeletal muscle (21), is overexpressed 1.8-fold. Although satellite cells may account for some portion of these alterations, additional cell populations are also likely involved.…”

Fibroblast Growth Factor-12 (FGF12) Translocation into Intestinal Epithelial Cells Is Dependent on a Novel Cell-penetrating Peptide Domain

“…Its translocation depends on binding with FGFR1 and FGFR4 (11) and requires phosphatidylinositol 3-kinase (PI3K) activity (12) and Hsp90 (13). Moreover, FGF1 can interact with intracellular proteins such as FIBP (14), p34 (15), casein kinase 2 (CK2) (16), and mortalin (17), suggesting that endocytosed FGF1 plays multiple roles inside cells. Interestingly, overexpression of the FGF12 gene down-regulated radiation-induced apoptosis in the human leukemic mast cell line HMC-1, indicating that FGF12 is able to inhibit radiation-induced tissue damage like other FGFs (18).…”

FGF-dependent left–right asymmetry patterning in zebrafish is mediated by Ier2 and Fibp1

“…These studies yielded fgf intra-cellular binding protein 1( fibp1) as a major interacting factor. Fibp1 is known to be a nuclear FGF binding protein, but as in the case of Ier2, its in vivo functions have not been elucidated (27,28). Ier2 is partly and Fipb1 is highly conserved among vertebrates (Figs.…”