Charting the molecular network of the drug target Bcr-Abl Export

@article{citeulike:4372551, abstract = {10.1073/pnas.0900653106 The tyrosine kinase Bcr-Abl causes chronic myeloid leukemia and is the cognate target of tyrosine kinase inhibitors like imatinib. We have charted the protein–protein interaction network of Bcr-Abl by a 2-pronged approach. Using a monoclonal antibody we have first purified endogenous Bcr-Abl protein complexes from the CML K562 cell line and characterized the set of most tightly-associated interactors by MS. Nine interactors were subsequently subjected to tandem affinity purifications/MS analysis to obtain a molecular interaction network of some hundred cellular proteins. The resulting network revealed a high degree of interconnection of 7 ” core” components around Bcr-Abl (Grb2, Shc1, Crk-I, c-Cbl, p85, Sts-1, and SHIP-2), and their links to different signaling pathways. Quantitative proteomics analysis showed that tyrosine kinase inhibitors lead to a disruption of this network. Certain components still appear to interact with Bcr-Abl in a phosphotyrosine-independent manner. We propose that Bcr-Abl and other drug targets, rather than being considered as single polypeptides, can be considered as complex protein assemblies that remodel upon drug action.}, author = {Brehme, Marc and Hantschel, Oliver and Colinge, Jacques and Kaupe, Ines and Planyavsky, Melanie and K\"{o}cher, Thomas and Mechtler, Karl and Bennett, Keiryn L. and Superti-Furga, Giulio}, citeulike-article-id = {4372551}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0900653106}, citeulike-linkout-1 = {http://www.pnas.org/content/0900653106v1//.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/0900653106v1//.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19380743}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19380743}, doi = {10.1073/pnas.0900653106}, journal = {Proceedings of the National Academy of Sciences}, keywords = {disease, network}, month = {May}, number = {18}, pages = {7414--7419}, posted-at = {2009-04-21 17:27:39}, priority = {2}, title = {Charting the molecular network of the drug target Bcr-Abl}, url = {http://dx.doi.org/10.1073/pnas.0900653106}, volume = {106}, year = {2009} }

TY - JOUR ID - citeulike:4372551 L3 - citeulike-article-id:4372551 N2 - 10.1073/pnas.0900653106 The tyrosine kinase Bcr-Abl causes chronic myeloid leukemia and is the cognate target of tyrosine kinase inhibitors like imatinib. We have charted the protein–protein interaction network of Bcr-Abl by a 2-pronged approach. Using a monoclonal antibody we have first purified endogenous Bcr-Abl protein complexes from the CML K562 cell line and characterized the set of most tightly-associated interactors by MS. Nine interactors were subsequently subjected to tandem affinity purifications/MS analysis to obtain a molecular interaction network of some hundred cellular proteins. The resulting network revealed a high degree of interconnection of 7 “core” components around Bcr-Abl (Grb2, Shc1, Crk-I, c-Cbl, p85, Sts-1, and SHIP-2), and their links to different signaling pathways. Quantitative proteomics analysis showed that tyrosine kinase inhibitors lead to a disruption of this network. Certain components still appear to interact with Bcr-Abl in a phosphotyrosine-independent manner. We propose that Bcr-Abl and other drug targets, rather than being considered as single polypeptides, can be considered as complex protein assemblies that remodel upon drug action. IS - 18 JF - Proceedings of the National Academy of Sciences EP - 7419 TI - Charting the molecular network of the drug target Bcr-Abl VL - 106 SP - 7414 KW - disease KW - network AU - Brehme, Marc AU - Hantschel, Oliver AU - Colinge, Jacques AU - Kaupe, Ines AU - Planyavsky, Melanie AU - Köcher, Thomas AU - Mechtler, Karl AU - Bennett, Keiryn AU - Superti-Furga, Giulio PY - 2009/05/05/ UR - http://dx.doi.org/10.1073/pnas.0900653106 ER -