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SRC directly phosphorylates Bif-1 and prevents its interaction with Bax and the initiation of anoikis

Hirohito Yamaguchi1, Nicholas T Woods, Jay F Dorsey

  • 1H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.

The Journal of Biological Chemistry
|May 14, 2008
PubMed

Insights

Bif-1 protein phosphorylation by c-Src kinase prevents its interaction with Bax, inhibiting apoptosis during anoikis. This reveals a novel mechanism for Src signaling in preventing cell death.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Bif-1 protein interacts with Bax to induce apoptosis, but the precise mechanism remains unclear.
  • Understanding Bif-1-Bax interaction is crucial for deciphering cell death pathways.

Purpose of the Study:

  • To elucidate the molecular mechanism regulating the interaction between Bif-1 and Bax.
  • To investigate the role of Bif-1 phosphorylation in apoptosis and anoikis.

Main Methods:

  • Investigated Bif-1 phosphorylation status under apoptotic stimuli.
  • Identified c-Src as the kinase phosphorylating Bif-1 at tyrosine 80.
  • Assessed the impact of Src-mediated phosphorylation on Bif-1-Bax interaction and Bax activation during anoikis.

Main Results:

  • Bif-1 phosphorylation is repressed by apoptotic stimuli.
  • c-Src directly phosphorylates Bif-1 on tyrosine 80.
  • Src phosphorylation of Bif-1 inhibits its binding to Bax, suppressing Bax activation and anoikis.

Conclusions:

  • Phosphorylation of Bif-1 by c-Src impairs its interaction with Bax, thereby inhibiting apoptosis.
  • This phosphorylation-dependent mechanism provides a novel way for Src oncogenic signaling to prevent cell death.

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