The EGFR signalling pathway in lipid rafts. See text for description of the pathway. The PLD shown here is PLD-2, which is activated directly by the EGFR. It must be also emphasised that at least three steps contribute to activation of Akt: (i) binding of PIP3/PI(3,4)P2 to its Pleckstrin Homology domain; (ii) phosphorylation on Thr308 by PDK1; and (iii) phosphorylation on Ser473. PLD: phospholipase D; PA: phosphatidic acid; PC: phosphatidylcholine; mTOR: mammalian target of rapamycin; EGFR: epidermal growth factor receptor; FKHR: Forkhead Box, subgroup O, transcription factors; CREB: cAMP response element binding protein; PDK1: 3-phosphoinositide-dependent kinase-1; PI3K: phosphatidylinositol 3-kinase; PIP2: phosphatidylinositol-4,5-bisphosphate; PI(3,4)P2: phosphatidylinositol-3,4-bisphosphate; PIP3: phosphatidylinositol-3,4,5,-trisphosphate; S6K1: ribosomal protein S6 kinase 1.