Cell-cycle dependent tyrosine phosphorylation on mortalin regulates its interaction with fibroblast growth factor-1.
We previously reported that endogenously expressed, intracellularly localized fibroblast growth factor (FGF)-1 interacts with mortalin. Here we report that FGF-1 added to the culture medium of quiescent BALB/c3T3 cells is taken up by the cells and interacts with mortalin in the cells in a regulated manner. Although both the internalized FGF-1 and mortalin were present at high levels throughout the FGF-1-initiated cell cycle, their interaction became apparent only in late G1 phase. Interestingly, mortalin was preferentially tyrosine phosphorylated at the same time, and when its normally weak phosphorylation in early G1 phase was augmented by treating the cells with vanadate, a strong interaction between mortalin and FGF-1 was established. Conversely, when phosphorylated mortalin was treated with tyrosine phosphatase, its interaction with FGF-1 was abrogated. These results indicate that FGF-1 taken up by cells preferentially interacts with mortalin in late G1 phase of the cell cycle, and that tyrosine phosphorylation of mortalin regulates this interaction.
Mizukoshi
E
E
National Institute of Bioscience and Human Technology, Tsukuba, Ibaraki, 305-8566, Japan.
Suzuki
M
M
Misono
T
T
Loupatov
A
A
Munekata
E
E
Kaul
S C
SC
Wadhwa
R
R
Imamura
T
T
D016475:3T3 Cells; D000818:Animals; D002352:Carrier Proteins; D002453:Cell Cycle; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism* / Q000493:pharmacokinetics; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D015151:Immunoblotting; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism*; D014638:Vanadates / Q000494:pharmacology
D002352:Carrier Proteins; D018840:HSP70 Heat-Shock Proteins; C083794:Hspa9 protein, mouse; C080352:mortalin; D016220:Fibroblast Growth Factor 1; D014638:Vanadates; D014443:Tyrosine; D004247:DNA