| Popis: |
Aurintricarboxylic acid (ATA) prevents apoptosis in a wide range of cell types, including PC12 cells. ATA isknown to increase the phosphorylation level of IGF-1 receptor (IGF-1R) and downstream signaling proteins.ATA can translocate across the plasma membrane of PC12 cells and inhibit protein tyrosine phosphatases(PTPs) and, therefore, it is not clear whether ATA exer ted its antiapoptotic effect through activation of IGF-1Ror by inhibition of cytosolic PTPs. When PC12 cells, deprived of serum, were treated with Fab fragment ofanti-IGF-1R antibody to prevent the binding of ATA to the extracellular domain of IGF-1R, ATA was foundto penetrate into the cytoso lic space of the cells. Unde r these conditions, the survival-promoting effects of ATAwere abolished, and the increase of phosphorylation and characteristic cleavage of IGF-1R were not observed.These results indicate that the antiapoptotic effect of ATA in PC12 cells is due to the binding of ATA to theextracellular domain of IGF-1R and subsequent activation of the IGF-1R, not inhibition of cytosolic PTP(s). |
