Fer kinase sustains the activation level of ERK1/2 and increases the production of VEGF in hypoxic cells

Yaniv Salem, Sally Shpungin, Orel Pasder, Oz Pomp, Michal Taler, Hana Malovani, Uri Nir

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Fer is a nuclear and cytoplasmic tyrosine kinase that is ubiquitously expressed in mammalian cells. Herein we show that Fer sustains a key signaling step in hypoxic cells. Knock-down of the Fer protein using a specific siRNA decreased the production of VEGF by the hypoxic cells. Conversely, ectopic expression of this kinase led to an elevated production of VEGF under hypoxia. At the molecular level, Fer was found to associate with ERK1/2 and this interaction was intensified under hypoxia. Moreover, Fer increased the activation levels of ERK1/2, and reducing the level of Fer, impaired the activation of ERK1/2 in hypoxic cells. Blocking the MEK-ERK1/2 signaling pathway with the MEK inhibitors U0126, or PD98059 led to the abrogation of ERK1/2 activity in hypoxic cells, an effect that was counteracted by Fer. Hence, Fer sustains the activation of ERK1/2 and increases the production of VEGF in hypoxic cells, without affecting the MEK-ERK signaling pathway.

Original languageEnglish
Pages (from-to)341-353
Number of pages13
JournalCellular Signalling
Volume17
Issue number3
DOIs
StatePublished - Mar 2005

Bibliographical note

Funding Information:
We thank Mrs. A. Goldreich for typing this manuscript. This work was supported by grants from CaPCURE Israel, from the Ministry of Health Research Fund, from the Wankslbaum Family Research Fund and from the Horowitz Foundation.

Keywords

  • ERK1/2
  • Fer kinase
  • HIF1α
  • Hypoxia
  • Signal transduction
  • VGF
  • siRNA

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