Fig. 3.

Two essential kinase systems in autophagy. A: class III phosphatidylinositol 3-kinase (PI3-kinase) complex. Vps34, a class III PI3-kinase, phosphorylates phosphatidylinositol (PI) to produce phosphatidylinositol 3-phosphate (PI3P), a docking lipid that promotes protein complex formation, membrane enclosing, and the consequent sequestration of cytoplasmic components in autophagic vacuoles. Vps34 forms complexes with and is regulated by beclin-1 and Vps15. Beclin-1 further interacts with and is regulated by Bcl-2, Ambra, and UVRAG. B: serine/threonine protein kinase complex. Regulation of this complex is centered on the interaction between Atg13 and Atg1, a serine/threonine protein kinase. In the presence of nutrients and growth factors, target of rapamycin (TOR) kinase is active and phosphorylates Atg13, preventing its association with Atg1. During starvation, TOR is not active, resulting in the activation of phosphatases and partial dephosphorylation of Atg13. Dephosphorylated Atg13 associates tightly with and activates Atg1, leading to the recruitment of Atg17 and the formation of the autophagic serine/threonine kinase complex.