Cell-cycle dependent tyrosine phosphorylation on mortalin regulates its interaction with fibroblast growth factor-1

We previously reported that endogenously expressed, intracellularly localiz ed 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 tak en 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 h igh levels throughout the FGF-l-initiated cell cycle, their interaction bec ame apparent only in late G1 phase. Interestingly, mortalin was preferentia lly tyrosine phosphorylated at the same time, and when its normally weak, p hosphorylation in early G1 phase was augmented by treating the cells with v anadate, a strong interaction between mortalin and FGF-1 was established. C onversely, when phosphorylated mortalin was treated with tyrosine phosphata se, its interaction with FGF-1 was abrogated. These results indicate that F GF-1 taken up by cells preferentially interacts with mortalin in late G1 ph ase of the cell cycle, and that tyrosine phosphorylation of mortalin regula tes this interaction. (C) 2001 Academic Press.