| First Author | Dou Z | Year | 2013 |
| Journal | Mol Cell | Volume | 50 |
| Issue | 1 | Pages | 29-42 |
| PubMed ID | 23434372 | Mgi Jnum | J:198150 |
| Mgi Id | MGI:5495594 | Doi | 10.1016/j.molcel.2013.01.022 |
| Citation | Dou Z, et al. (2013) Class IA PI3K p110beta subunit promotes autophagy through Rab5 small GTPase in response to growth factor limitation. Mol Cell 50(1):29-42 |
| abstractText | Autophagy is an evolutionarily conserved membrane trafficking process. Induction of autophagy in response to nutrient limitation or cellular stress occurs by similar mechanisms in organisms from yeast to mammals. Unlike yeast, metazoan cells rely more on growth factor signaling for a wide variety of cellular activities including nutrient uptake. How growth factor availability regulates autophagy is poorly understood. Here we show that, upon growth factor limitation, the p110beta catalytic subunit of the class IA phosphoinositide 3-kinases (PI3Ks) dissociates from growth factor receptor complexes and increases its interaction with the small GTPase Rab5. This p110beta-Rab5 association maintains Rab5 in its guanosine triphosphate (GTP)-bound state and enhances the Rab5-Vps34 interaction that promotes autophagy. p110beta mutants that fail to interact with Rab5 are defective in autophagy promotion. Hence, in mammalian cells, p110beta acts as a molecular sensor for growth factor availability and induces autophagy by activating a Rab5-mediated signaling cascade. |
