dc.contributor.author | Breitkopf, Susanne B. | en_US |
dc.contributor.author | Yang, Xuemei | en_US |
dc.contributor.author | Begley, Michael J. | en_US |
dc.contributor.author | Kulkarni, Meghana | en_US |
dc.contributor.author | Chiu, Yu-Hsin | en_US |
dc.contributor.author | Turke, Alexa B. | en_US |
dc.contributor.author | Lauriol, Jessica | en_US |
dc.contributor.author | Yuan, Min | en_US |
dc.contributor.author | Qi, Jie | en_US |
dc.contributor.author | Engelman, Jeffrey A. | en_US |
dc.contributor.author | Hong, Pengyu | en_US |
dc.contributor.author | Kontaridis, Maria I. | en_US |
dc.contributor.author | Cantley, Lewis C. | en_US |
dc.contributor.author | Perrimon, Norbert | en_US |
dc.contributor.author | Asara, John M. | en_US |
dc.date.accessioned | 2016-03-01T19:48:28Z | |
dc.date.issued | 2016 | en_US |
dc.identifier.citation | Breitkopf, S. B., X. Yang, M. J. Begley, M. Kulkarni, Y. Chiu, A. B. Turke, J. Lauriol, et al. 2016. “A Cross-Species Study of PI3K Protein-Protein Interactions Reveals the Direct Interaction of P85 and SHP2.” Scientific Reports 6 (1): 20471. doi:10.1038/srep20471. http://dx.doi.org/10.1038/srep20471. | en |
dc.identifier.issn | 2045-2322 | en |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:25658315 | |
dc.description.abstract | Using a series of immunoprecipitation (IP) – tandem mass spectrometry (LC-MS/MS) experiments and reciprocal BLAST, we conducted a fly-human cross-species comparison of the phosphoinositide-3-kinase (PI3K) interactome in a drosophila S2R+ cell line and several NSCLC and human multiple myeloma cell lines to identify conserved interacting proteins to PI3K, a critical signaling regulator of the AKT pathway. Using H929 human cancer cells and drosophila S2R+ cells, our data revealed an unexpected direct binding of Corkscrew, the drosophila ortholog of the non-receptor protein tyrosine phosphatase type II (SHP2) to the Pi3k21B (p60) regulatory subunit of PI3K (p50/p85 human ortholog) but no association with Pi3k92e, the human ortholog of the p110 catalytic subunit. The p85-SHP2 association was validated in human cell lines, and formed a ternary regulatory complex with GRB2-associated-binding protein 2 (GAB2). Validation experiments with knockdown of GAB2 and Far-Western blots proved the direct interaction of SHP2 with p85, independent of adaptor proteins and transfected FLAG-p85 provided evidence that SHP2 binding on p85 occurred on the SH2 domains. A disruption of the SHP2-p85 complex took place after insulin/IGF1 stimulation or imatinib treatment, suggesting that the direct SHP2-p85 interaction was both independent of AKT activation and positively regulates the ERK signaling pathway. | en |
dc.language.iso | en_US | en |
dc.publisher | Nature Publishing Group | en |
dc.relation.isversionof | doi:10.1038/srep20471 | en |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4738311/pdf/ | en |
dash.license | LAA | en_US |
dc.title | A Cross-Species Study of PI3K Protein-Protein Interactions Reveals the Direct Interaction of P85 and SHP2 | en |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en |
dc.relation.journal | Scientific Reports | en |
dash.depositing.author | Breitkopf, Susanne B. | en_US |
dc.date.available | 2016-03-01T19:48:28Z | |
dc.identifier.doi | 10.1038/srep20471 | * |
dash.authorsordered | false | |
dash.contributor.affiliated | Lauriol, J | |
dash.contributor.affiliated | Yuan, Min | |
dash.contributor.affiliated | Breitkopf, Susanne B. | |
dash.contributor.affiliated | Asara, John | |
dash.contributor.affiliated | Engelman, Jeffrey A | |
dash.contributor.affiliated | Kontaridis, Maria | |
dash.contributor.affiliated | Perrimon, Norbert | |