Optimal lysophosphatidic acid-induced DNA synthesis and cell migration but not survival require intact autophosphorylation sites of the epidermal growth factor receptor.

The Journal of Biological Chemistry
Wenlin DengGabor Tigyi

Abstract

Lysophosphatidic acid (LPA)-elicited transphosphorylation of receptor tyrosine kinases has been implicated in mediating extracellular signal-regulated kinase (ERK) 1/2 activation, which is necessary for LPA-induced cell proliferation, migration, and survival. B82L cells lack epidermal growth factor receptor (EGFR) but express LPA(1-3), platelet-derived growth factor (PDGF), ErbB2, and insulin-like growth factor receptor transcripts, yet LPA caused no detectable transphosphorylation of these receptor tyrosine kinases. LPA equally protected B82L cells, or transfectants expressing EGFR, the kinase dead EGFR(K721A), EGFR(Y5F) receptor mutant, which lacks five autophosphorylation sites, or EGFR(Y845F), which lacks the Src phosphorylation site from tumor necrosis factor-alpha-induced apoptosis. In contrast, LPA-elicited DNA synthesis and migration were augmented in cells expressing EGFR, EGFR(K721A), or EGFR(Y845F), but not EGFR(Y5F), although the PDGF responses were indistinguishable. LPA-induced transphosphorylation of the EGFR, ErbB2, or PDGF receptor was not required for its antiapoptotic effect. EGFR with or without intrinsic kinase activity or without the Src-phosphorylation site augmented, but was not required for, LPA-elicite...Continue Reading

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Citations

Jul 3, 2009·The Journal of Biological Chemistry·Deepti ChaturvediTarun B Patel
Nov 7, 2012·Biochimica Et Biophysica Acta·Gyöngyi N KissGabor Tigyi
Sep 8, 2012·Biochimica Et Biophysica Acta·David N BrindleyGabor J Tigyi
Dec 12, 2007·The Journal of Biological Chemistry·Francis Edwin, Tarun B Patel
Sep 29, 2018·International Journal of Molecular Sciences·Hanne LeysenStuart Maudsley

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