Proto-Oncogenic Src Phosphorylates EB1 to Regulate the Microtubule-Focal Adhesion Crosstalk and Stimulate Cell

Yijun Zhang1, Youguang Luo1, Rui Lyu1

  • 1State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.

Theranostics
|October 5, 2016
PubMed

Insights

The proto-oncogenic protein Src regulates cell migration by phosphorylating end-binding protein 1 (EB1), impacting microtubule dynamics and focal adhesions. This discovery clarifies molecular mechanisms driving tumor metastasis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Cell migration is crucial for tumor progression and metastasis.
  • The crosstalk between microtubules (MTs) and focal adhesions (FAs) is vital for cell migration.
  • Molecular mechanisms regulating MT-FA crosstalk remain largely unknown.

Purpose of the Study:

  • To identify key molecular players regulating MT-FA crosstalk.
  • To elucidate the role of the proto-oncogenic protein Src in this process.
  • To investigate the interaction between Src and end-binding protein 1 (EB1).

Main Methods:

  • Investigated Src interaction and phosphorylation of EB1 in vitro and in cells.
  • Utilized systematic mutagenesis to identify the specific phosphorylation site on EB1 (Y247).
  • Examined the localization of Src and phosphorylated EB1.
  • Assessed the impact of EB1 phosphorylation on its interactions with other plus-end tracking proteins (+TIPs) and MT dynamics.

Main Results:

  • Src directly interacts with and phosphorylates EB1 at tyrosine-247 (Y247).
  • Both activated Src and Y247-phosphorylated EB1 localize to centrosomes and FAs.
  • Src-mediated EB1 phosphorylation reduces its binding to other +TIPs (APC, MCAK).
  • EB1 phosphorylation at Y247 accelerates MT catastrophe and enhances cell migration.

Conclusions:

  • The Src-EB1 signaling axis is a critical regulator of MT-FA crosstalk.
  • Src-mediated phosphorylation of EB1 promotes cell migration by altering MT dynamics.
  • This pathway represents a potential therapeutic target for inhibiting tumor metastasis.

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