ErbB protein modifications are secondary to severe cell membrane alterations induced by elisidepsin treatment

摘要: Elisidepsin is a marine-derived anti-tumor agent with unique mechanism of action. It has been suggested to induce necrosis associated severe membrane damage. Since indirect evidence points the involvement ErbB receptor tyrosine kinases and lipid rafts in action elisidepsin, we investigated effect drug on distribution proteins systematically compared elisidepsin sensitivity cell lines overexpressing receptors. Stable expression single member family (ErbB1-3) or co-transfection ErbB2 ErbB3 did not modify CHO A431 cells. However, induced redistribution two GPI-anchored (transfected eGFP placental alkaline phosphatase) from plasma intracellular vesicles without comparable effects ErbB1 ErbB2. increased binding conformational sensitive anti-ErbB3 antibody modifying other antibodies, it decreased homoassociation both ErbB3. We also found that fluorescence anisotropy specific fluorescent probe blue shift emission spectrum Laurdan pointing significant changes order possibly formation liquid ordered domains. Although preferentially altered by our data question their role determining drug. assume induction domains primary leading all observed changes.