1. Diverse injurious stimuli reduce protein tyrosine phosphatase-μμ expression and enhance epidermal growth factor receptor signaling in human airway epithelia.
- Author
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Hyun, Sang W., Anglin, Ian E., Liu, Anguo, Yang, Shiqi, Sorkin, John D., Lillehoj, Erik, Tonks, Nicholas K., Passaniti, Antonino, and Goldblum, Simeon E.
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PROTEIN-tyrosine kinases , *GENE expression , *EPIDERMAL growth factor receptors , *EPITHELIAL cells , *AUTOPHOSPHORYLATION , *CELLULAR signal transduction , *PHOSPHOLIPASES - Abstract
In response to injury, airway epithelia utilize an epidermal growth factor (EGF) receptor (EGFR) signaling program to institute repair and restitution. Protein tyrosine phosphatases (PTPs) counterregulate EGFR autophosphorylation and downstream signaling. PTPμμ is highly expressed in lung epithelia and can be localized to intercellular junctions where its ectodomain homophilically interacts with PTPμμ ectodomain expressed on neighboring cells. We asked whether PTPμμ expression might be altered in response to epithelial injury and whether altered PTPμμ expression might influence EGFR signaling. In A549 cells, diverse injurious stimuli dramatically reduced PTPμμ protein expression. Under basal conditions, small interfering RNA (siRNA)-induced silencing of PTPμμ increased EGFR Y992 and Y1068 phosphorylation. In the presence of EGF, PTPμμ knockdown increased EGFR Y845, Y992, Y1045, Y1068, Y1086, and Y1173 but not Y1148 phosphorylation. Reduced PTPμμ expression increased EGF-stimulated phosphorylation of Y992, a docking site for phospholipase C (PLC)γγ1, activation of PLCγγ1 itself, and increased cell migration in both wounding and chemotaxis assays. In contrast, overexpression of PTPμμ decreased EGF-stimulated EGFR Y992 and Y1068 phosphorylation. Therefore, airway epithelial injury profoundly reduces PTPμμ expression, and PTPμμ depletion selectively increases phosphorylation of specific EGFR tyrosine residues, PLCγγ1 activation, and cell migration, providing a novel mechanism through which epithelial integrity may be restored. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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