Substrate‐dependent control of MAPK phosphorylation in vivo |
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| Authors: | Yoosik Kim Ze'ev Paroush Knud Nairz Ernst Hafen Gerardo Jiménez Stanislav Y Shvartsman |
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| Institution: | 1. Lewis‐Sigler Institute for Integrative Genomics, Princeton University, , Princeton, NJ, USA;2. Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel‐Canada, Faculty of Medicine, Hebrew University, , Jerusalem, Israel;3. Institute of Molecular Systems Biology, ETH, , Zurich, Switzerland;4. Institut de Biologia Molecular de Barcelona‐CSIC and Institució Catalana de Recerca i Estudis Avan?ats, Parc Científic de Barcelona, , Barcelona, Spain |
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| 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. |
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