alpha(1)-Adrenergic receptor stimulation of cell motility requires phospholipase D-mediated extracellular

Rachel L Sang1, Jessica F Johnson, Jennifer Taves

  • 1Department of Bioscience, Minnesota State University Moorhead, Moorhead, MN 56563, USA.

Insights

Phenylephrine activates the extracellular signal-regulated kinase (ERK) pathway via phospholipase D (PLD) in fibroblasts. This PLD-dependent ERK activation promotes cell migration and stress fiber formation, crucial for early cellular events.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Signal Transduction

Background:

  • Phospholipase D (PLD) is implicated in tumorigenesis and cellular events like invasion and migration.
  • The role of PLD in growth factor signaling pathways remains incompletely understood.

Purpose of the Study:

  • To investigate the role of phospholipase D in phenylephrine-induced signaling in CCL39 fibroblasts.
  • To elucidate the involvement of PLD in the activation of the extracellular signal-regulated kinase (ERK) pathway.

Main Methods:

  • Utilized phenylephrine as an alpha(1)-adrenergic receptor agonist.
  • Assessed ERK phosphorylation, stress fiber formation, and wound healing rates.
  • Employed 1-butanol and PD98059 (MEK inhibitor) to probe the pathway.
  • Investigated the effects of exogenously added phosphatidic acid.

Main Results:

  • Phenylephrine significantly increased ERK phosphorylation and stress fiber formation.
  • PLD inhibition with 1-butanol blocked phenylephrine-induced ERK activation and stress fiber formation.
  • Phenylephrine enhanced wound healing, an effect reversed by MEK inhibition.
  • Exogenous phosphatidic acid mimicked phenylephrine's effects on ERK and stress fibers.

Conclusions:

  • Phospholipase D plays a novel and essential role in activating the ERK growth factor pathway.
  • PLD-mediated ERK activation by phenylephrine is critical for stimulating early cellular events like stress fiber formation and wound healing.

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