May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
Corneal Epithelial Cell Motility Is Triggered by Activation of the Epidermal Growth Factor Receptor Through Phosphatidic Acid Signaling
Author Affiliations & Notes
  • J.K. Klarlund
    Ophthal & Vis Sci Res Ctr, Univ of Pittsburgh Eye & Ear Inst, Pittsburgh, PA
  • A.R. Mazie
    Ophthal & Vis Sci Res Ctr, Univ of Pittsburgh Eye & Ear Inst, Pittsburgh, PA
  • J.K. Spix
    Ophthal & Vis Sci Res Ctr, Univ of Pittsburgh Eye & Ear Inst, Pittsburgh, PA
  • E.R. Block
    Ophthal & Vis Sci Res Ctr, Univ of Pittsburgh Eye & Ear Inst, Pittsburgh, PA
  • Footnotes
    Commercial Relationships  J.K. Klarlund, None; A.R. Mazie, None; J.K. Spix, None; E.R. Block, None.
  • Footnotes
    Support  NIH grant EY013463 and EY08098,and grants from Research to Prevent Blindness, and The Eye and Ear Foundation (Pittsburgh, PA)
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 5035. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      J.K. Klarlund, A.R. Mazie, J.K. Spix, E.R. Block; Corneal Epithelial Cell Motility Is Triggered by Activation of the Epidermal Growth Factor Receptor Through Phosphatidic Acid Signaling . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5035.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract
 
Purpose:
 

There is great interest in understanding the signals that induce motility in corneal epithelial cells, since signaling pathways are attractive pharmacological targets. We have previously shown that induction of motility upon wounding is strictly dependent on activation of the epidermal growth factor receptor (EGFR) through proteolytic activation of the precursor for one of its ligands (proHB–EGF). The purpose of these studies was to identify signals that lead to EGFR activation.

 
Methods:
 

The studies relied on a previously published wounding assay that allows biochemical analysis of processes induced by wounding. Phospholipase D activities were assayed by labeling cells with [3H]myristic acid, adding 1–BuOH, and measuring formation of phosphatidylinositol butanol. Addition of short chain, water–soluble analogues of phosphatidic acid was used as a means of stimulating phosphatidic acid signaling.

 
Results:
 

Wounding activates phospholipase D, an enzyme that catalyzes the hydrolysis of phosphatidylcholine to generate phosphatidic acid. Short–chain analogues of phosphatidic acid induce motility robustly in corneal and other epithelial cell types, and we provide evidence that phosphatidic acid acts directly on one or more cellular targets. Phosphatidic acid was found to trigger transactivation of the epidermal growth factor receptor via proHB–EGF cleavage. This is surprising because phospholipase D has so far been considered a downstream target for the EGFR. Inhibition of phosphatidic acid signaling in the presence of EGF indicated that EGFR activation is not sufficient for induction of motility, and that phosphatidic acid has additional signaling activities.

 
Conclusions:
 

These observations, together with other data, lead us to suggest that stimulation of phospholipase D is an immediate consequence of wounding, and that the EGFR is activated through phospholipase D activation. We propose the following signaling circuitry for induction of motility in corneal epithelial cells (PLD: phospholipase D; PA: phosphatidic acid; ERK: extracelular regulated kinase):  

 
Keywords: wound healing • signal transduction • cornea: basic science 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×