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

Wenlin Deng, Helen Poppleton, Satoshi Yasuda, Natalia Makarova, Yoriko Shinozuka, De An Wang, Leonard R. Johnson, Tarun B. Patel, Gabor Tigyi

Research output: Contribution to journalArticle

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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 LPA1-3, 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 EGFRK721A, EGFRY5F receptor mutant, which lacks five autophosphorylation sites, or EGFRY845F, which lacks the Src phosphorylation site from tumor necrosis factor-α-induced apoptosis. In contrast, LPA-elicited DNA synthesis and migration were augmented in cells expressing EGFR, EGFRK721A, or EGFRY845F, but not EGFRY5F, 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-elicited cell proliferation or migration. In B82L cells, augmentation of these two LPA responses required intact autophosphorylation sites because among the four EGFR mutants, only cells expressing the EGFRY5F mutant showed no enhancement. In EGFRY5F-expressing cells, LPA failed to elicit tyrosine phosphorylation of Src homologous and collagen protein (SHC) and caused only a modest increase in ERK1/2 phosphorylation similar to that in wild-type B82L cells. The present data pinpoint the lack of importance of the intrinsic kinase activity in contrast to the importance of autophosphorylation sites of the EGFR for SHC phosphorylation in the enhancement of select ERK1/2-dependent LPA responses.

Original languageEnglish (US)
Pages (from-to)47871-47880
Number of pages10
JournalJournal of Biological Chemistry
Volume279
Issue number46
DOIs
StatePublished - Nov 12 2004

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Epidermal Growth Factor Receptor
Cell Movement
Phosphorylation
DNA
Platelet-Derived Growth Factor
Cell proliferation
Receptor Protein-Tyrosine Kinases
Phosphotransferases
Collagen
Cells
Cell Proliferation
lysophosphatidic acid
Somatomedin Receptors
Platelet-Derived Growth Factor Receptors
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Tyrosine
Cell Survival
Proteins
Tumor Necrosis Factor-alpha

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Optimal lysophosphatidic acid-induced DNA synthesis and cell migration but not survival require intact autophosphorylation sites of the epidermal growth factor receptor. / Deng, Wenlin; Poppleton, Helen; Yasuda, Satoshi; Makarova, Natalia; Shinozuka, Yoriko; Wang, De An; Johnson, Leonard R.; Patel, Tarun B.; Tigyi, Gabor.

In: Journal of Biological Chemistry, Vol. 279, No. 46, 12.11.2004, p. 47871-47880.

Research output: Contribution to journalArticle

Deng, Wenlin ; Poppleton, Helen ; Yasuda, Satoshi ; Makarova, Natalia ; Shinozuka, Yoriko ; Wang, De An ; Johnson, Leonard R. ; Patel, Tarun B. ; Tigyi, Gabor. / Optimal lysophosphatidic acid-induced DNA synthesis and cell migration but not survival require intact autophosphorylation sites of the epidermal growth factor receptor. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 46. pp. 47871-47880.
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AU - Tigyi, Gabor

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