Related Experiment Video
Updated: Mar 14, 2026

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells
Published on: July 20, 2014
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.
Abstract:
Cell migration, a complex process critical for tumor progression and metastasis, requires a dynamic crosstalk between microtubules (MTs) and focal adhesions (FAs). However, the molecular mechanisms underlying this event remain elusive. Herein we identify the proto-oncogenic protein Src as an important player in the regulation of the MT-FA crosstalk. Src interacts with and phosphorylates end-binding protein 1 (EB1), a member of MT plus end-tracking proteins (+TIPs), both in cells and in vitro. Systematic mutagenesis reveals that tyrosine-247 (Y247) is the primary residue of EB1 phosphorylated by Src. Interestingly, both constitutively activated Src and Y247-phosphorylated EB1 localize to the centrosome and FAs. Src-mediated EB1 phosphorylation diminishes its interactions with other +TIPs, including adenomatous polyposis coli (APC) and mitotic centromere associated kinesin (MCAK). In addition, EB1 phosphorylation at Y247 enhances the rate of MT catastrophe and significantly stimulates cell migration. These findings thus demonstrate that the Src-EB1 axis plays a crucial role in regulating the crosstalk between MTs and FAs to promote cell migration.
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.
Related Concept Videos
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
MAPK Signaling Cascades
PI3K/mTOR/AKT Signaling Pathway
Cytoskeletal Coordination in Cell Migration
Mitogens and the Cell Cycle
mTOR Signaling and Cancer Progression
The mTOR pathway or the...

