%0 Journal Article %1 Newman2013Construction %A Newman, Robert H. %A Hu, Jianfei %A Rho, Hee-Sool S. %A Xie, Zhi %A Woodard, Crystal %A Neiswinger, John %A Cooper, Christopher %A Shirley, Matthew %A Clark, Hillary M. %A Hu, Shaohui %A Hwang, Woochang %A Jeong, Jun Seop S. %A Wu, George %A Lin, Jimmy %A Gao, Xinxin %A Ni, Qiang %A Goel, Renu %A Xia, Shuli %A Ji, Hongkai %A Dalby, Kevin N. %A Birnbaum, Morris J. %A Cole, Philip A. %A Knapp, Stefan %A Ryazanov, Alexey G. %A Zack, Donald J. %A Blackshaw, Seth %A Pawson, Tony %A Gingras, Anne-Claude C. %A Desiderio, Stephen %A Pandey, Akhilesh %A Turk, Benjamin E. %A Zhang, Jin %A Zhu, Heng %A Qian, Jiang %D 2013 %I Nature Publishing Group %J Molecular systems biology %K networks phosphorylation signalling %N 1 %R 10.1038/msb.2013.12 %T Construction of human activity-based phosphorylation networks. %U http://dx.doi.org/10.1038/msb.2013.12 %V 9 %X The landscape of human phosphorylation networks has not been systematically explored, representing vast, unchartered territories within cellular signaling networks. Although a large number of in vivo phosphorylated residues have been identified by mass spectrometry (MS)-based approaches, assigning the upstream kinases to these residues requires biochemical analysis of kinase-substrate relationships (KSRs). Here, we developed a new strategy, called CEASAR, based on functional protein microarrays and bioinformatics to experimentally identify substrates for 289 unique kinases, resulting in 3656 high-quality KSRs. We then generated consensus phosphorylation motifs for each of the kinases and integrated this information, along with information about in vivo phosphorylation sites determined by MS, to construct a high-resolution map of phosphorylation networks that connects 230 kinases to 2591 in vivo phosphorylation sites in 652 substrates. The value of this data set is demonstrated through the discovery of a new role for PKA downstream of Btk (Bruton's tyrosine kinase) during B-cell receptor signaling. Overall, these studies provide global insights into kinase-mediated signaling pathways and promise to advance our understanding of cellular signaling processes in humans.

@article{Newman2013Construction, abstract = {The landscape of human phosphorylation networks has not been systematically explored, representing vast, unchartered territories within cellular signaling networks. Although a large number of in vivo phosphorylated residues have been identified by mass spectrometry ({MS})-based approaches, assigning the upstream kinases to these residues requires biochemical analysis of kinase-substrate relationships ({KSRs}). Here, we developed a new strategy, called {CEASAR}, based on functional protein microarrays and bioinformatics to experimentally identify substrates for 289 unique kinases, resulting in 3656 high-quality {KSRs}. We then generated consensus phosphorylation motifs for each of the kinases and integrated this information, along with information about in vivo phosphorylation sites determined by {MS}, to construct a high-resolution map of phosphorylation networks that connects 230 kinases to 2591 in vivo phosphorylation sites in 652 substrates. The value of this data set is demonstrated through the discovery of a new role for {PKA} downstream of Btk (Bruton's tyrosine kinase) during B-cell receptor signaling. Overall, these studies provide global insights into kinase-mediated signaling pathways and promise to advance our understanding of cellular signaling processes in humans.}, added-at = {2018-12-02T16:09:07.000+0100}, author = {Newman, Robert H. and Hu, Jianfei and Rho, Hee-Sool S. and Xie, Zhi and Woodard, Crystal and Neiswinger, John and Cooper, Christopher and Shirley, Matthew and Clark, Hillary M. and Hu, Shaohui and Hwang, Woochang and Jeong, Jun Seop S. and Wu, George and Lin, Jimmy and Gao, Xinxin and Ni, Qiang and Goel, Renu and Xia, Shuli and Ji, Hongkai and Dalby, Kevin N. and Birnbaum, Morris J. and Cole, Philip A. and Knapp, Stefan and Ryazanov, Alexey G. and Zack, Donald J. and Blackshaw, Seth and Pawson, Tony and Gingras, Anne-Claude C. and Desiderio, Stephen and Pandey, Akhilesh and Turk, Benjamin E. and Zhang, Jin and Zhu, Heng and Qian, Jiang}, biburl = {https://www.bibsonomy.org/bibtex/217f4129a2b3ccf6f7cd21b43c6645618/karthikraman}, citeulike-article-id = {12237347}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/msb.2013.12}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/msb201312}, citeulike-linkout-2 = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3658267/}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/23549483}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=23549483}, day = 02, doi = {10.1038/msb.2013.12}, interhash = {e8a36e5afd61ba160c720b2ad8b93508}, intrahash = {17f4129a2b3ccf6f7cd21b43c6645618}, issn = {1744-4292}, journal = {Molecular systems biology}, keywords = {networks phosphorylation signalling}, month = apr, number = 1, pmcid = {PMC3658267}, pmid = {23549483}, posted-at = {2013-06-14 05:58:16}, priority = {2}, publisher = {Nature Publishing Group}, timestamp = {2018-12-02T16:09:07.000+0100}, title = {Construction of human activity-based phosphorylation networks.}, url = {http://dx.doi.org/10.1038/msb.2013.12}, volume = 9, year = 2013 }