EGFR and β1-Integrins utilise different signalling pathways to activate Akt
2008 (English)In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 314, no 2, 309-316 p.Article in journal (Refereed) Published
Akt, also called PKB, is a serine/threonine kinase that plays a major role in cell survival. It can be activated by several cellular receptors, including integrins and growth factor receptors, in PI3K-dependent manners. In this study, we analyzed the two current models for Akt activation upon β1 integrin-mediated adhesion: via focal adhesion kinase and via transactivation of the EGF receptor. Distinct differences in the pathways leading to phosphorylation and activation of Akt from stimulated β1 integrins and EGF receptor were observed, including opposing sensitivity to the tyrosine kinase inhibitors PP2 and Gefitinib. Using knockout cells and integrin mutant cells, we show that β1 integrins can induce phosphorylation of Akt at Ser473 and Thr308 and Akt kinase activity independently of the EGF receptor activity, focal adhesion kinase, and the Src family members. In contrast to stimulation with EGF, β1 integrin-mediated adhesion did not induce Akt tyrosine phosphorylation. Moreover, tyrosine phosphorylation of Akt was found not to be required for its catalytic activity. The results identify a previously unrecognized mechanism by which β1 integrins activate the PI3K/Akt pathway.
Place, publisher, year, edition, pages
2008. Vol. 314, no 2, 309-316 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-96243DOI: 10.1016/j.yexcr.2007.08.018OAI: oai:DiVA.org:uu-96243DiVA: diva2:170750