title: SRC directly phosphorylates Bif-1 and prevents its interaction with Bax and the initiation of anoikis.
abstract: 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.
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Woods
authors.forename: Jay F
authors.initials: JF
authors.lastname: Dorsey
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Gjertsen
authors.forename: Timothy
authors.initials: T
authors.lastname: Yeatman
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.forename: Hong-Gang
authors.initials: HG
authors.lastname: Wang
mesh_terms: 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*
chemical_list: 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)