Figure 1: Schematic of PI3-kinase and PIP3 signaling. Regeneration-associated receptors activate intracellular enzymes including phosphoinositide 3-kinase (PI3K). PI3K converts PIP2 into PIP3, which in turn acts as a secondary messenger in multiple signaling cascades that influence axon growth and regeneration, among other important cellular functions. Phosphatase and tensin homolog (PTEN) is an important negative regulator of PI3K signaling by dephosphorylation of PIP3 to PIP2. The phosphates (P) on both phosphatidylinositols are shown in the schematic, in which the phosphate on the D3-position of PIP3 is highlighted in green. PIP3 generation recruits proteins with PH-, PX-, or FYVE domains to the plasma membrane and regulates their activity. The activation state of small GTPase Arf6 regulates axonal transport of regeneration-associated receptors, while small GTPases Cdc42 and Rac1 influence the cytoskeleton. The recruitment and activation of Akt by PIP3 is well established. Akt activates mTOR and subsequently activates S6K1 and the phosphorylation of ribosomal protein S6. The mTOR complex also inactivates 4E-BP1, which in turn influences eIF-4E to regulate transcription and translation. Akt also inhibits GSK3 that activates transcription factor Smad1 and inhibits CRMP2, among the regulation of other proteins. Akt also influences the activation state of SSH1, which is upstream of ADF/cofilin, and Cortactin to regulate cytoskeleton dynamics.