We have expressed the human p85β in chicken embryo fibroblasts (CEF) using the RCAS retroviral vector. At low concentrations, RCAS-p85β induces the formation of distinct foci of transformed cells. CEF transfected with high concentrations of RCAS-p85β show enhanced cell proliferation and PI3K signaling. RCAS-p85β shares this growth promoting potential with the cancer-derived mutants of p85α, but the wild type p85α protein expressed by the RCAS vector lacks this potential. The transforming and signaling activities of p85β depend on the PI3K catalytic subunit p110. We have used p110 isoform-specific inhibitors to show that the transforming and signaling activities of p85β can be mediated by p110α or p110β or both. This is in contrast to the transforming mutants of p85α which depend almost exclusively on p110α for their growth-promoting effect. p85β can be phosphorylated at Y655. Mutations of the phosphorylation site Y655A or Y655E lose almost all of their transforming and enhanced signaling activity. This result indicates that p85β could be subject to control by tyrosine kinases. Our data document important differences between p85α and p85β and suggest that p85β could carry out special functions in signaling and in cancer.
This work was supported by NIH Grant R01 CA078230. This is abstract 26049 of The Scripps Research Institute.
Citation Format: Yoshihiro Ito, Jonathan R. Hart, Lynn Ueno, Peter K. Vogt. The regulatory subunit of PI3K, p85β, induces cellular transformation, enhanced cell proliferation and increased PI3K signaling. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3339. doi:10.1158/1538-7445.AM2014-3339