| First Author | Yazlovitskaya EM | Year | 2015 |
| Journal | Mol Biol Cell | Volume | 26 |
| Issue | 10 | Pages | 1857-74 |
| PubMed ID | 25808491 | Mgi Jnum | J:244155 |
| Mgi Id | MGI:5912934 | Doi | 10.1091/mbc.E14-07-1203 |
| Citation | Yazlovitskaya EM, et al. (2015) Integrin alpha3beta1 regulates kidney collecting duct development via TRAF6-dependent K63-linked polyubiquitination of Akt. Mol Biol Cell 26(10):1857-74 |
| abstractText | The collecting system of the kidney develops from the ureteric bud (UB), which undergoes branching morphogenesis, a process regulated by multiple factors, including integrin-extracellular matrix interactions. The laminin (LM)-binding integrin alpha3beta1 is crucial for this developmental program; however, the LM types and LM/integrin alpha3beta1-dependent signaling pathways are poorly defined. We show that alpha3 chain-containing LMs promote normal UB branching morphogenesis and that LM-332 is a better substrate than LM-511 for stimulating integrin alpha3beta1-dependent collecting duct cell functions. We demonstrate that integrin alpha3beta1-mediated cell adhesion to LM-332 modulates Akt activation in the developing collecting system and that Akt activation is PI3K independent but requires decreased PTEN activity and K63-linked polyubiquitination. We identified the ubiquitin-modifying enzyme TRAF6 as an interactor with the integrin beta1 subunit and regulator of integrin alpha3beta1-dependent Akt activation. Finally, we established that the developmental defects of TRAF6- and integrin alpha3-null mouse kidneys are similar. Thus K63-linked polyubiquitination plays a previously unrecognized role in integrin alpha3beta1-dependent cell signaling required for UB development and may represent a novel mechanism whereby integrins regulate signaling pathways. |
