Exogenously added fibroblast growth factor 2 (FGF-2) to NIH3T3 cells interacts with nuclear ribosomal S6 kinase 2 (RSK2) in a cell cycle-dependent manner

J Biol Chem. 2005 Jul 8;280(27):25604-10. doi: 10.1074/jbc.M500232200. Epub 2005 May 6.

Abstract

Fibroblast growth factor 2 (FGF-2) has been detected in the nuclei of many tissues and cell lines. Here we demonstrate that FGF-2 added exogenously to NIH3T3 cells enters the nucleus and interacts with the nuclear active 90-kDa ribosomal S6 kinase 2 (RSK2) in a cell cycle-dependent manner. By using purified proteins, FGF-2 is shown to directly interact through two separate domains with two RSK2 domains on both sides of the hydrophobic motif, namely the NH2-terminal kinase domain (residues 360-381) by amino acid Ser-117 and the COOH-terminal kinase domain (residues 388-400) by amino acids Leu-127 and Lys-128. Moreover, this interaction leads to maintenance of the sustained activation of RSK2 in G1 phase of the cell cycle. FGF-2 mutants (FGF-2 S117A, FGF-2 L127A, and FGF-2 K128A) that fail to interact in vitro with RSK2 fail to maintain a sustained RSK2 activity in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites / genetics
  • COS Cells
  • Chlorocebus aethiops
  • Fibroblast Growth Factor 2 / chemistry
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 2 / pharmacology*
  • In Vitro Techniques
  • Mice
  • Molecular Sequence Data
  • Mutation
  • NIH 3T3 Cells
  • Protein Structure, Tertiary
  • Resting Phase, Cell Cycle / drug effects*
  • Resting Phase, Cell Cycle / physiology
  • Ribosomal Protein S6 Kinases, 90-kDa / chemistry
  • Ribosomal Protein S6 Kinases, 90-kDa / metabolism*
  • S Phase / drug effects*
  • S Phase / physiology

Substances

  • Fibroblast Growth Factor 2
  • Ribosomal Protein S6 Kinases, 90-kDa
  • ribosomal protein S6 kinase, 90kDa, polypeptide 3