%0 Journal Article %1 Kim2011Substratedependent %A Kim, Yoosik %A Paroush, Ze'ev %A Nairz, Knud %A Hafen, Ernst %A Jimenez, Gerardo %A Shvartsman, Stanislav Y. %D 2011 %I Nature Publishing Group %J Molecular Systems Biology %K phosphorylation signalling %R 10.1038/msb.2010.121 %T Substrate-dependent control of MAPK phosphorylation in vivo %U http://dx.doi.org/10.1038/msb.2010.121 %V 7 %X Phosphorylation of the mitogen-activated protein kinase (MAPK) is essential for its enzymatic activity and ability to control multiple substrates inside a cell. According to the current models, control of MAPK phosphorylation is independent of its substrates, which are viewed as mere sensors of MAPK activity. Contrary to this modular view of MAPK signaling, our studies in the Drosophila embryo demonstrate that substrates can regulate the level of MAPK phosphorylation in vivo. We demonstrate that a twofold change in the gene dosage of a single substrate can induce a significant change in the phosphorylation level of MAPK and in the conversion of other substrates. Our results support a model where substrates of MAPK counteract its dephosphorylation by phosphatases. Substrate-dependent control of MAPK phosphorylation is a manifestation of a more general retroactive effect that should be intrinsic to all networks with covalent modification cycles.

@article{Kim2011Substratedependent, abstract = {Phosphorylation of the mitogen-activated protein kinase ({MAPK}) is essential for its enzymatic activity and ability to control multiple substrates inside a cell. According to the current models, control of {MAPK} phosphorylation is independent of its substrates, which are viewed as mere sensors of {MAPK} activity. Contrary to this modular view of {MAPK} signaling, our studies in the Drosophila embryo demonstrate that substrates can regulate the level of {MAPK} phosphorylation in vivo. We demonstrate that a twofold change in the gene dosage of a single substrate can induce a significant change in the phosphorylation level of {MAPK} and in the conversion of other substrates. Our results support a model where substrates of {MAPK} counteract its dephosphorylation by phosphatases. Substrate-dependent control of {MAPK} phosphorylation is a manifestation of a more general retroactive effect that should be intrinsic to all networks with covalent modification cycles.}, added-at = {2018-12-02T16:09:07.000+0100}, author = {Kim, Yoosik and Paroush, Ze'ev and Nairz, Knud and Hafen, Ernst and Jimenez, Gerardo and Shvartsman, Stanislav Y.}, biburl = {https://www.bibsonomy.org/bibtex/2de6ba5cdaa126e8d75303a25f700662a/karthikraman}, citeulike-article-id = {8739235}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/msb.2010.121}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/msb2010121}, day = 01, doi = {10.1038/msb.2010.121}, interhash = {3232b8f68edc40bcf658db281d91adb6}, intrahash = {de6ba5cdaa126e8d75303a25f700662a}, journal = {Molecular Systems Biology}, keywords = {phosphorylation signalling}, month = feb, posted-at = {2011-02-02 10:16:04}, priority = {2}, publisher = {Nature Publishing Group}, timestamp = {2018-12-02T16:09:07.000+0100}, title = {Substrate-dependent control of {MAPK} phosphorylation in vivo}, url = {http://dx.doi.org/10.1038/msb.2010.121}, volume = 7, year = 2011 }