UV activates growth factor receptors via reactive oxygen intermediates

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Ultraviolet (UV) irradiation is a known cellular stressor.
• UV exposure rapidly induces the expression of the early growth response-1 (Egr-1) gene.
• Egr-1 encodes a transcription factor involved in cell survival pathways.

Purpose of the Study:

• To elucidate the signaling pathways involved in UV-induced Egr-1 gene expression.
• To investigate the role of reactive oxygen intermediates (ROI) and growth factor receptors in this process.

Main Methods:

• Utilized mouse NIH 3T3 fibroblasts and HC11 mouse mammary cells.
• Investigated tyrosine phosphorylation of epidermal growth factor receptor (EGFR) after UVC irradiation.
• Assessed the formation of signaling complexes involving EGFR using immunoprecipitation.
• Examined the effects of antioxidants, suramin, and dominant-negative EGFR on UV-induced signaling.

Main Results:

• UVC irradiation induced tyrosine phosphorylation and activation of EGFR.
• UV-induced EGFR activation was blocked by antioxidants, suramin, and dominant-negative EGFR.
• Hydrogen peroxide (H2O2) mimicked UV-induced EGFR activation, suggesting a role for ROI upstream of EGFR.
• UV irradiation led to the formation of signaling complexes between activated EGFR and downstream adaptors (SOS, Grb2, PLCγ, SHC).

Conclusions:

• Reactive oxygen intermediates (ROI) play a critical role in the early signaling events following UV irradiation.
• Activation of growth factor receptors, particularly EGFR, by ROI is an essential pathway for UV-induced Egr-1 expression.
• This pathway involving ROI and EGFR contributes to the cellular response to UV damage and promotes cell survival.