SRC directly phosphorylates Bif-1 and prevents its interaction with Bax and the initiation of anoikis.
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.
Yamaguchi
Hirohito
H
H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.
Woods
Nicholas T
NT
Dorsey
Jay F
JF
Takahashi
Yoshinori
Y
Gjertsen
Nicole R
NR
Yeatman
Timothy
T
Wu
Jie
J
Wang
Hong-Gang
HG
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D023102:Anoikis / Q000502:physiology*; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D011485:Protein Binding / Q000502:physiology; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C494826:BAX protein, human; C494827:Bax protein, mouse; C429293:SH3GLB1 protein, human; C486100:Sh3glb1 protein, mouse; D051028:bcl-2-Associated X Protein; D016392:Proto-Oncogene Proteins pp60(c-src)