Exogenously Added Fibroblast Growth Factor 2 (FGF-2) to NIH3T3 Cells Interacts with Nuclear Ribosomal S6 Kinase 2 (RSK2) in a Cell Cycle-dependentManner*
Résumé
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.
Mots clés
FGF-2
fibroblast growth factor 2
B-FGF-2
biotinylated FGF-2
CK2
casein kinase 2
CTK
carboxyl-terminal kinase
FGFR
FGF receptor
FCS
fetal calf serum
HA
hemagglutinin
HM
hydrophobic motif
MAP
mitogen-activated protein
MOPS
4-morpholinepropanesulfonic acid
MSK
mitogen and stressactivated protein kinase
NTK
NH 2 -terminal kinase
RSK
90-kDa ribosomal S6 protein kinase
WT
wild type
Domaines
Sciences du Vivant [q-bio]| Origine | Fichiers éditeurs autorisés sur une archive ouverte |
|---|