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Author Spotlight: Developing Tools to Tune the Activity of Tyrosine Phosphatases
06:56

Author Spotlight: Developing Tools to Tune the Activity of Tyrosine Phosphatases

Published on: September 6, 2024

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SRC Kinase-Mediated Tyrosine Phosphorylation of TUBB3 Regulates Its Stability and Mitotic Spindle Dynamics in

Alan Alfano1, Jin Xu1, Xi Yang1

  • 1Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Pharmaceutics
|May 28, 2022
PubMed

Insights

Prostate cancer cells show Class III β-tubulin (TUBB3) is phosphorylated by c-SRC, impacting protein stability and spindle function. This discovery may lead to new biomarkers for cancer recurrence and treatment failure.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Biochemistry

Background:

  • Tubulin, particularly β-tubulin, is crucial for cellular functions and a target for cancer drugs like taxanes.
  • Class III β-tubulin (TUBB3) is linked to taxane resistance and poor prognosis in solid cancers.
  • The role of tyrosine kinase c-Src in modulating tubulin function remains unclear.

Purpose of the Study:

  • To investigate the phosphorylation of TUBB3 by c-SRC in prostate cancer.
  • To elucidate how c-SRC-mediated phosphorylation affects TUBB3 stability and localization.
  • To understand the impact of TUBB3 phosphorylation on cellular processes like mitosis and spindle stability.

Main Methods:

  • Prostate cancer cell lines were used to study TUBB3 phosphorylation.
  • Immunoprecipitation and Western blotting were employed to detect and analyze TUBB3 phosphorylation at Tyrosine 340 (Y340).
  • SRC kinase inhibitors were used to assess the functional consequences of Y340 phosphorylation on spindle stability during mitosis.

Main Results:

  • TUBB3 was identified as a direct phosphorylation substrate of c-SRC at Y340 in prostate cancer cells.
  • Y340 phosphorylation was found to regulate TUBB3 protein stability and its subcellular distribution.
  • Inhibition of SRC kinase activity led to compromised spindle stability in mitotic cells, partly due to reduced TUBB3 Y340 phosphorylation.

Conclusions:

  • c-SRC directly phosphorylates TUBB3 at Y340, influencing its stability and localization in prostate cancer cells.
  • TUBB3 Y340 phosphorylation is critical for maintaining spindle stability during mitosis.
  • Understanding TUBB3 post-translational modifications by c-SRC could reveal novel biomarkers for predicting cancer recurrence and treatment outcomes.
Keywords:
SRC kinaseTUBB3drug resistancemicrotubuleprostate cancertubulintyrosine phosphorylation

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