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.
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.
Soulet
Fabienne
F
Laboratoire de Biologie Vasculaire, Institut de Pharmacologie et de Biologie Structurale, Unité Mixte de Recherche 5089, 205 Route de Narbonne, 31077 Toulouse, France.
Bailly
Karine
K
Roga
Stéphane
S
Lavigne
Anne-Claire
AC
Amalric
François
F
Bouche
Gérard
G
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D019556:COS Cells; D002522:Chlorocebus aethiops; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D066298:In Vitro Techniques; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D041681:NIH 3T3 Cells; D017434:Protein Structure, Tertiary; D016192:Resting Phase, Cell Cycle / Q000187:drug effects* / Q000502:physiology; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000737:chemistry / Q000378:metabolism*; D016196:S Phase / Q000187:drug effects* / Q000502:physiology
D016222:Fibroblast Growth Factor 2; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3