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dc.contributor.authorBreitkopf, Susanne B.en_US
dc.contributor.authorYang, Xuemeien_US
dc.contributor.authorBegley, Michael J.en_US
dc.contributor.authorKulkarni, Meghanaen_US
dc.contributor.authorChiu, Yu-Hsinen_US
dc.contributor.authorTurke, Alexa B.en_US
dc.contributor.authorLauriol, Jessicaen_US
dc.contributor.authorYuan, Minen_US
dc.contributor.authorQi, Jieen_US
dc.contributor.authorEngelman, Jeffrey A.en_US
dc.contributor.authorHong, Pengyuen_US
dc.contributor.authorKontaridis, Maria I.en_US
dc.contributor.authorCantley, Lewis C.en_US
dc.contributor.authorPerrimon, Norberten_US
dc.contributor.authorAsara, John M.en_US
dc.date.accessioned2016-03-01T19:48:28Z
dc.date.issued2016en_US
dc.identifier.citationBreitkopf, 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.issn2045-2322en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:25658315
dc.description.abstractUsing 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.isoen_USen
dc.publisherNature Publishing Groupen
dc.relation.isversionofdoi:10.1038/srep20471en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4738311/pdf/en
dash.licenseLAAen_US
dc.titleA Cross-Species Study of PI3K Protein-Protein Interactions Reveals the Direct Interaction of P85 and SHP2en
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalScientific Reportsen
dash.depositing.authorBreitkopf, Susanne B.en_US
dc.date.available2016-03-01T19:48:28Z
dc.identifier.doi10.1038/srep20471*
dash.authorsorderedfalse
dash.contributor.affiliatedBreitkopf, Susanne B.
dash.contributor.affiliatedLauriol, J
dash.contributor.affiliatedYuan, Min
dash.contributor.affiliatedAsara, John
dash.contributor.affiliatedKontaridis, Maria
dash.contributor.affiliatedEngelman, Jeffrey A
dash.contributor.affiliatedPerrimon, Norbert


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