Rapid changes in the phosphoproteome show diverse cellular responses following stimulation of human lung fibroblasts

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Development of an In Vitro Assay to Evaluate Contractile Function of Mesenchymal Cells that Underwent Epithelial-Mesenchymal Transition
06:02

Development of an In Vitro Assay to Evaluate Contractile Function of Mesenchymal Cells that Underwent Epithelial-Mesenchymal Transition

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Corinne Stannard1, Vukic Soskic, Jasminka Godovac-Zimmermann

  • 1Centre for Molecular Medicine, Department of Medicine, University College London, United Kingdom.

Biochemistry
|November 26, 2003
PubMed

Insights

Endothelin-1 rapidly triggers protein changes in lung fibroblasts, influencing cell cycle and other functions. This study proposes a model for how endothelin-1 promotes cell growth, offering insights into its mitogenic effects.

Area of Science:

  • Cellular Biology
  • Molecular Signaling
  • Biochemistry

Background:

  • Endothelin receptors A and B (ET_A and ET_B) mediate cellular responses.
  • Endothelin-1 (ET-1) is a potent vasoconstrictor and mitogen.
  • Understanding ET-1 signaling is crucial for various physiological and pathological processes.

Purpose of the Study:

  • To investigate the rapid protein phosphorylation and dephosphorylation events downstream of ET_A and ET_B receptors.
  • To identify proteins involved in ET-1-mediated cellular responses.
  • To propose a model for ET-1's role in cell cycle progression.

Main Methods:

  • Stimulation of human lung fibroblasts with endothelin-1.
  • Analysis of protein phosphorylation and dephosphorylation.
  • Identification of key signaling proteins.

Main Results:

  • Observed rapid changes in phosphorylation of proteins regulating cell cycle, cytoskeleton, ion channels, transcription, angiogenesis, and metabolism.
  • Identified specific proteins like protein phosphatase 2A, CDC25 A, and caspase-2 precursor.
  • Detected phosphorylation of diverse proteins within 2 minutes of ET-1 stimulation.

Conclusions:

  • A model for ET-1-induced cell cycle progression is proposed based on observed protein changes.
  • ET-1 rapidly engages a wide array of cellular signaling pathways.
  • Findings provide insights into the mitogenic mechanisms of ET-1.

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