Obligatory role of Src kinase in the signaling mechanism for TRPC3 cation channels

Related Experiment Video

Updated: Aug 23, 2026

Expression and Purification of the Human Lipid-sensitive Cation Channel TRPC3 for Structural Determination by Single-particle Cryo-electron Microscopy
08:27

Expression and Purification of the Human Lipid-sensitive Cation Channel TRPC3 for Structural Determination by Single-particle Cryo-electron Microscopy

Published on: January 7, 2019

Guillermo Vazquez1, Barbara J Wedel, Brian T Kawasaki

  • 1Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA. vazquez@niehs.nih.gov

The Journal of Biological Chemistry
|July 24, 2004
PubMed

Insights

Src kinases are essential for activating TRPC3 channels through receptor and diacylglycerol signaling. This finding highlights a crucial role for tyrosine kinases in regulating calcium (Ca2+) entry.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Ion Channel Physiology

Background:

  • Canonical transient receptor potential (TRPC) channels, particularly TRPC3, are implicated in calcium (Ca2+) entry.
  • TRPC3 can be activated by diacylglycerol (DAG) independent of calcium store depletion.
  • Limited knowledge exists regarding other receptor-dependent modulators of TRPC3 activity.

Purpose of the Study:

  • To investigate the role of tyrosine kinases in the activation of TRPC3 channels.
  • To determine if tyrosine kinases mediate receptor- and diacylglycerol-dependent TRPC3 activation.

Main Methods:

  • Utilized HEK293 cells stably expressing TRPC3.
  • Employed pharmacological inhibition of tyrosine kinases, specifically Src kinases.
  • Investigated TRPC3 activity using dominant-negative Src mutants and Src-deficient cell lines.
  • Restored TRPC3 regulation by expressing wild-type Src.

Main Results:

  • Pharmacological inhibition of tyrosine kinases, including Src, abolished TRPC3 activation by muscarinic receptor stimulation and DAG.
  • TRPC3 regulation was lost in cells expressing a dominant-negative Src mutant or in Src-deficient cells.
  • Re-expression of wild-type Src restored TRPC3 regulation in these conditions.

Conclusions:

  • Src kinases play an obligatory role in the activation of TRPC3 channels.
  • Receptor- and diacylglycerol-dependent activation of TRPC3 requires Src kinase activity.
  • This study elucidates a key signaling pathway for TRPC3 channel function.

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