Interferon gamma-dependent transactivation of epidermal growth factor receptor

• Published in: FEBS letters 2007-04, Vol.581 (7), p.1475-1480
• Main Authors: Burova, Elena, Vassilenko, Konstantin, Dorosh, Victoria, Gonchar, Ilya, Nikolsky, Nikolai
• Format: Article
• Language: English
• Subjects: a disintegrin and metalloprotease; ADAM; EGF; EGFR; Enzyme Activation; epidermal growth factor; Epidermal growth factor receptor; ERK; extracellular signal-regulated kinase; G-protein coupled receptor; GPCR; growth hormone; HB-EGF; HeLa Cells; heparin-binding EGF like growth factor; Humans; IFNγ; IFNγR; interferon gamma; interferon gamma receptor; Interferon-gamma - pharmacology; interleukine; JAK; Janus kinase; Janus Kinase 2 - antagonists & inhibitors; MAPK; mitogen-activated protein kinase; Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 3 - metabolism; Phosphorylation; proline-rich tyrosine kinase 2; Protein Kinase Inhibitors - pharmacology; Pyk2; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - metabolism; signal transducer and activator of transcription; Signal Transduction; src-Family Kinases - antagonists & inhibitors; STAT; STAT1; STAT1 Transcription Factor - metabolism; TGF-α; Transactivation; Transcriptional Activation - drug effects; transforming growth factor-α; Tyrosine phosphorylation
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2007.03.002

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.