Interferon gamma-dependent transactivation of epidermal growth factor receptor

Abstract 

The present report provides evidence that, in A431 cells, interferon γ (IFNγ) induces the rapid (within 5min), and reversible, tyrosine phosphorylation of the epidermal growth factor receptor (EGFR). IFNγ-induced EGFR transactivation requires EGFR kinase activity, as well as activity of the Src-family tyrosine kinases and JAK2. Here, we show that IFNγ-induced STAT1 activation in A431 and HeLa cells partially depends on the kinase activity of both EGFR and Src. Furthermore, in these cells, EGFR kinase activity is essential for IFNγ-induced ERK1,2 activation. This study is the first to demonstrate that EGFR is implicated in IFNγ-dependent signaling pathways.

Abbreviations: EGF, epidermal growth factor, EGFR, epidermal growth factor receptor, IFNγ, interferon gamma, IFNγR, interferon gamma receptor, JAK, Janus kinase, STAT, signal transducer and activator of transcription, TGF-α, transforming growth factor-α, HB-EGF, heparin-binding EGF like growth factor, GPCR, G-protein coupled receptor, MAPK, mitogen-activated protein kinase, ERK, extracellular signal-regulated kinase, ADAM, a disintegrin and metalloprotease, GH, growth hormone, IL, interleukine, Pyk2, proline-rich tyrosine kinase 2

Keywords: IFNγ, Transactivation, Epidermal growth factor receptor, STAT1, Tyrosine phosphorylation