Extracellular ATP stimulates epithelial cell motility through Pyk2-mediated activation of the EGF receptor

► ATP activates the EGF receptor and cell motility through signaling by Src family kinases (SFKs). ► Pyk2 is rapidly activated by stimulation with exogenous ATP. ► Blocking Pyk2 function inhibits SFKs and EGF receptor activation. ► Blocking Pyk2 function also inhibits ATP-stimulated healing of wounds in cell sheets. ► Pyk2 mediates ATP-induced activation of the SFKs, the EGF receptor, and the enhanced cell motility.