“…Transactivation of the EGF receptor (EGFR) by TGF- 1 can also stimulate PI3 kinase and Akt (22,36,37,52). This has been linked to Smad-induced increases in the synthesis of the EGF receptor ligands (36), such as heparin-binding EGF, stimulation of c-Src-family kinases (22,37), induction of NADPH oxidase (36,37), PKC (52), and activation of TNF-␣-converting enzyme (TACE), which leads to the shedding of EGFR ligands (37).…”