The PI3K/PTEN/Akt/mTOR and Raf/MEK/ERK PI3K/PTEN/Akt/mTOR and pathways are regulated by upstream growth factor and mitogen receptors as well as Ras and various kinases. Many kinases serve to phosphorylate S/T and Y residues on Raf and S/T residues on Akt. Some of the Raf phosphorylation events serve to enhance its activity (shown by a black P in a white circle) whereas others serve to inhibit its activity (shown by a white P in a black circle. Moreover there are phosphatases such as PP2A, PTEN, SHIP and PHLPP, which remove phosphates on certain regulatory residues on Raf, MEK, ERK, PtdIns(3,4,5)P3 and Akt as well as other signaling molecules. The PI3K/Akt pathway is also activated after receptor ligation. Akt and ERK have many downstream targets which serve to regulate cell growth and apoptosis. Some of the downstream transcription factors regulated by these pathways are indicated in diamond shaped outlines.