@article {760301,
	title = {A Cross-Species Study of PI3K Protein-Protein Interactions Reveals the Direct Interaction of P85 and SHP2.},
	journal = {Sci Rep},
	volume = {6},
	year = {2016},
	month = {2016},
	pages = {20471},
	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.

},
	issn = {2045-2322},
	doi = {10.1038/srep20471},
	author = {Breitkopf, Susanne B and Yang, Xuemei and Begley, Michael J and Kulkarni, Meghana and Chiu, Yu-Hsin and Turke, Alexa B and Lauriol, Jessica and Yuan, Min and Qi, Jie and Engelman, Jeffrey A and Hong, Pengyu and Kontaridis, Maria I and Cantley, Lewis C and Perrimon, Norbert and Asara, John M}
}
