Differential activation of the Ras/extracellular-signal-regulated protein kinase pathway is responsible for the biological consequences induced by the Axl receptor tyrosine kinase

Yih Woei C Fridell, Yan Jin, Lawrence Quilliam, Andreas Burchert, Patrick Mccloskey, Gwendolyn Spizz, Brian Varnum, Channing Der, Edison T. Liu

Research output: Contribution to journalArticle

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Abstract

To understand the mechanism of Axl signaling, we have initiated studies to delineate downstream components in interleukin-3-dependent 32D cells by using a chimeric receptor containing the recombinant epidermal growth factor (EGF) receptor extracellular and transmembrane domains and the Axl kinase domain (EAK [for EGF receptor-Axl kinase]). We have previously shown that upon exogenous EGF stimulation, 32D-EAK cells are capable of proliferation in the absence of interleukin-3. With this system, we determined that EAK-induced cell survival and mitogenesis are dependent upon the Ras/extracellular-signal-regulated protein kinase (ERK) cascade. Although the phosphatidylinositol-3 kinase pathway is activated upon EAK signaling, it appears to be dispensable for the biological actions of the Axl kinase. Furthermore, we demonstrated that different threshold levels of Ras/ERK activation are needed to induce a block to apoptosis or proliferation in 32D cells. Recently, we have identified an Axl ligand, GAS6. Surprisingly, GAS6-stimulated 32D-Axl cells exhibited no blockage to apoptosis or mitogenic response which is correlated with the absence of Ras/ERK activation. Taken together, these data suggest that different extracellular domains dramatically alter the intracellular response of the Axl kinase. Furthermore, our data suggest that the GAS6-Axl interaction does not induce mitogenesis and that its exact role remains to be determined.

Original languageEnglish (US)
Pages (from-to)135-145
Number of pages11
JournalMolecular and Cellular Biology
Volume16
Issue number1
StatePublished - Jan 1996
Externally publishedYes

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Extracellular Signal-Regulated MAP Kinases
Protein Kinases
Phosphotransferases
Interleukin-3
Epidermal Growth Factor Receptor
Phosphatidylinositol 3-Kinase
Apoptosis
Epidermal Growth Factor
Cell Survival
Cell Proliferation
Ligands
axl receptor tyrosine kinase

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

Cite this

Differential activation of the Ras/extracellular-signal-regulated protein kinase pathway is responsible for the biological consequences induced by the Axl receptor tyrosine kinase. / Fridell, Yih Woei C; Jin, Yan; Quilliam, Lawrence; Burchert, Andreas; Mccloskey, Patrick; Spizz, Gwendolyn; Varnum, Brian; Der, Channing; Liu, Edison T.

In: Molecular and Cellular Biology, Vol. 16, No. 1, 01.1996, p. 135-145.

Research output: Contribution to journalArticle

Fridell, Yih Woei C ; Jin, Yan ; Quilliam, Lawrence ; Burchert, Andreas ; Mccloskey, Patrick ; Spizz, Gwendolyn ; Varnum, Brian ; Der, Channing ; Liu, Edison T. / Differential activation of the Ras/extracellular-signal-regulated protein kinase pathway is responsible for the biological consequences induced by the Axl receptor tyrosine kinase. In: Molecular and Cellular Biology. 1996 ; Vol. 16, No. 1. pp. 135-145.
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