Epithelial cell motility is triggered by activation of the EGF receptor through phosphatidic acid signaling.
Phospholipase D catalyzes the hydrolysis of phosphatidylcholine to generate phosphatidic acid, and there is currently much interest in elucidating messenger functions for this molecule. We report here that wounding sheets of corneal epithelial and Madin Darby canine kidney cells induces strong activation of phospholipase D, and we provide evidence that activation is amplified through a positive feed-back loop. Short-chain analogues of phosphatidic acid induce motility robustly in corneal and other epithelial cell types. The effects of these analogues were not the result of their conversion to the corresponding diacylglycerol or lysophosphatidic acid, implying that phosphatidic acid acts directly on one or more cellular targets. Strikingly, phosphatidic acid signaling was found to stimulate the epidermal growth factor receptor (EGFR) through a transactivation process. Healing of wounds in sheets of corneal epithelial cells is absolutely dependent on epidermal growth factor receptor signaling, and the present data suggest that its activation is a result of wound-induced phospholipase D activation.
Ophthalmology and Visual Sciences Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Abigail R
AR
Mazie
Julie K
JK
Spix
Ethan R
ER
Block
Hewa B
HB
Achebe
Jes K
JK
Klarlund
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D019573:Epithelium, Corneal / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D010712:Phosphatidic Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010739:Phospholipase D / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction; D014945:Wound Healing
D015815:Cell Adhesion Molecules; D010712:Phosphatidic Acids; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011493:Protein Kinase C; D010739:Phospholipase D