NUCLEAR ACCUMULATION OF FIBROBLAST GROWTH-FACTOR RECEPTORS IS REGULATED BY MULTIPLE SIGNALS IN ADRENAL-MEDULLARY CELLS

In an effort to determine the localization of fibroblast growth factor (FGF) receptors (FGFR) that could mediate the intracellular action of FGF-2, we discovered the presence of high-affinity FGF-2 binding site s in the nuclei of bovine adrenal medullary cells (BAMC). Western blot analysis demonstrated the presence of 103-, 118-, and 145-kDa forms o f FGFR1 in nuclei isolated from BAMC. I-125-FGF-2 cross-linking to nuc lear extracts followed by FGFR1 immunoprecipitation showed that FGFR1 can account for the nuclear FGF-2 binding sites. Nuclear FGFR1 has kin ase activity and undergoes autophosphorylation. Immunocytochemistry wi th the use of confocal and electron microscopes demonstrated the prese nce of FGFR1 within the nuclear interior. Nuclear subfractionation fol lowed by Western blot or immunoelectron microscopic analysis showed th at the nuclear FGFR1 is contained in the nuclear matrix and the nucleo plasm. Agents that induce translocation of endogenous FGF-2 to the nuc leus (forskolin, carbachol, or angiotensin II) increased the intranucl ear accumulation of FGFR1. This accumulation was accompanied by an ove rall increase in FGF-2-inducible tyrosine kinase activity. Our finding s suggest a novel mode for growth factor action whereby growth factor receptors translocate to the nucleus in parallel with their ligand and act as direct mediators of nuclear responses to cell stimulation.