ADP-ribosylation Factor 4 Small GTPase Mediates Epidermal Growth Factor Receptor-dependent Phospholipase D2 Activation

摘要: The epidermal growth factor receptor (EGFR) plays a critical role in the development, proliferation, and differentiation of cells epithelial mesenchymal origin. These EGFR-dependent cellular processes are mediated by repertoire intracellular signaling pathways triggered activation EGFR cytoplasmic domain, which originates from ligand binding its extracellular domain. To understand molecular mechanisms domain transmits mitogenic messages to downstream pathways, we used region as bait yeast two-hybrid screening. We found that ADP-ribosylation 4 (ARF4) interacts with part mediates EGF-dependent phospholipase D2 (PLD2) but does not mediate PLD1. In addition, ARF4-mediated PLD2 leads dramatic transcription activator protein 1 (AP-1), and, importantly, ARF4 activity is required for EGF-induced AP-1. Our findings indicate molecule directly regulates this stimulates AP-1-dependent response.