Nuclear and cytoplasmic localization of different basic fibroblast growth factor species

Abstract

The subcellular distribution of basic fibroblastic growth factor (bFGF) was analyzed by subcellular fractionation and immunofluorescence to gain insight into potential mechanisms for its release from cells. Subcellular fractionation of either SK-Hep-1 cells or NIH 3T3 cells transfected with a bFGF cDNA revealed that the 18 kd form of bFGF was found primarily in the cytosolic fraction, whereas the 22 and 24 kd forms of bFGF were found preferentially in ribosomal and nuclear fractions. Analysis of bFGF distribution by immunofluorescence using an antibody that recognized all forms of bFGF indicated both cytoplasmic and nuclear localization but failed to reveal any growth factor in structures representing secretory vesicles. Therefore, bFGF has a distribution inconsistent with that of a secretory protein.

Endogenous basic fibroblast growth factor isoforms involved in different intracellular protein complexes

“…The subcellular localization of the different bFGF isoforms was confirmed in CHO cell lines and has previously been described for the SK-Hep1 cell [9]. We showed that the 210-aa bFGF in the transfected CHO cells was nuclear whereas the 155-aa form was mainly cytoplasmic.…”

“…We showed that the 210-aa bFGF in the transfected CHO cells was nuclear whereas the 155-aa form was mainly cytoplasmic. Several studies of endogenous bFGF in SKHep1 cells revealed that the 18 kDa form is found primarily in the cytosolic fraction, whereas the 22 and 24 kDa forms occur preferentially in the ribosomal and nuclear fractions [9]. A recent report has shown a tight association of each bFGF isoform with polyribosomes but the distinct targets, rRNA or proteins, were not characterized [28].…”

“…The AUG-initiated protein is cytoplasmic, whereas the CUG-initiated forms are nuclear [8,9]. A specific role in oncogenesis for the CUG-initiated bFGF forms has been proposed [10,11].…”

Fibroblast growth factor-binding protein expression changes with disease progression in clinical and experimental human squamous epithelium

“…1 It is a potent mitogen for cultured cells of mesenchymal, neuroectodermal, neural crest and ectodermal (keratinocyte) origin. 2 Four isoforms of bFGF are derived from alternative initiation of translation at 3 CUG start codons, which are larger (22, 22.5 and 24 kDa) 3 and contain a nuclear localization sequence (NLS) 4,5 near the NH 2 terminus, 6 and 1 AUG start codon, which is smaller (18 kDa), lacks an NLS and is primarily cytosolic. 4,7 Both aFGF and bFGF lack a signal sequence to direct their secretion through the endoplasmic reticulum (ER) and Golgi apparatus.…”

Molecular atherectomy for restenosis

“…The largest of these products are translocated into the nucleus, where they are associated with the chromatin and nucleoli (Renko et al 1990. Smaller FGF peptides are exported from the cell by some mechanism yet unknown (since they lack a signal peptide) (Abraham et al 1986) and apparently stored in the extracellular matrix, from which they can be released-at least in tissue culture-by heparin, heparinase, plasmin, or an extracellular phospholipase C .…”