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LPA regulates EGFR binding in airway epithelial cells via ERK and PKC
Author(s) -
Kassel Karen M,
Jacobs Anna C,
Toews Myron L
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a428-c
Subject(s) - ionomycin , mapk/erk pathway , lysophosphatidic acid , phosphorylation , protein kinase c , chemistry , microbiology and biotechnology , mek inhibitor , kinase , bapta , epidermal growth factor , receptor , biology , biochemistry , intracellular
We showed that lysophosphatidic acid (LPA) induces a rapid and sustained decrease in EGF receptor (EGFR) binding in BEAS‐2B airway epithelial cells ( FASEB J 19:A527). We hypothesized that the rapid and sustained decreases would be mediated by different signaling pathways. BEAS‐2B cells were treated for 15 min or 18 hr and then incubated with 125 I‐EGF on ice to measure cell surface EGFR binding. Cells were also treated for 5 min and assessed for ERK phosphorylation. LPA, the direct PKC activator PMA, and the Ca 2+ ionophore ionomycin caused rapid and sustained decreases in EGFR binding and stimulated ERK phosphorylation. The MEK inhibitor U0126 blocked ERK phosphorylation and the 15‐min decrease in binding for LPA, PMA, and ionomycin, but not the 18‐hr decrease in binding. PKC inhibition blocked the 15‐min decrease in binding and ERK phosphorylation by PMA and ionomycin, but only slightly inhibited LPA. In contrast, PKC inhibition completely blocked the 18‐hr decrease in binding by LPA, PMA, and ionomycin. The Ca 2+ chelator BAPTA‐AM blocked the ionomycin‐induced rapid decrease in EGFR binding and ERK phosphorylation, but not that induced by LPA or PMA. These data confirm that LPA uses distinct mechanisms to mediate the rapid vs sustained decreases in EGFR binding in BEAS‐2B cells. The rapid decrease is primarily mediated via MEK/ERK whereas the sustained decrease involves PKC. Supported by an AHA fellowship to KMK and by NE DHHS .