Yamaguchi Hirohito, Woods Nicholas T, Dorsey Jay F, Takahashi Yoshinori, Gjertsen Nicole R, Yeatman Timothy, Wu Jie, Wang Hong-Gang
H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.
J Biol Chem. 2008 Jul 4;283(27):19112-8. doi: 10.1074/jbc.M709882200. Epub 2008 May 12.
Bif-1 interacts with Bax and enhances its conformational rearrangement, resulting in apoptosis. However, the molecular mechanism governing the interaction between Bif-1 and Bax is poorly defined. Here we provide evidence that Bif-1 is phosphorylated, an event that can be repressed by apoptotic stimuli. The protein kinase c-Src binds to and directly phosphorylates Bif-1 on tyrosine 80. Moreover, Src phosphorylation of Bif-1 suppresses the interaction between Bif-1 and Bax, resulting in the inhibition of Bax activation during anoikis. Together, these results suggest that phosphorylation of Bif-1 impairs its binding to Bax and represses apoptosis, providing another mechanism by which Src oncogenic signaling can prevent cell death.
Bif-1与Bax相互作用并增强其构象重排，从而导致细胞凋亡。然而，关于Bif-1与Bax之间相互作用的分子机制仍不清楚。在此，我们提供证据表明Bif-1会发生磷酸化，这一事件可被凋亡刺激所抑制。蛋白激酶c-Src与Bif-1结合并直接使其酪氨酸80位点磷酸化。此外，Bif-1的Src磷酸化抑制了Bif-1与Bax之间的相互作用，导致在失巢凋亡过程中Bax激活受到抑制。这些结果共同表明，Bif-1的磷酸化会损害其与Bax的结合并抑制细胞凋亡，这为Src致癌信号传导阻止细胞死亡提供了另一种机制。
