title: Substrate-dependent control of MAPK phosphorylation in vivo.
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.
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Yoosik
authors.initials: Y
authors.lastname: Kim
authors.forename: Ze'ev
authors.initials: Z
authors.lastname: Paroush
authors.forename: Knud
authors.initials: K
authors.lastname: Nairz
authors.forename: Ernst
authors.initials: E
authors.lastname: Hafen
authors.forename: Gerardo
authors.initials: G
authors.lastname: Jiménez
authors.forename: Stanislav Y
authors.initials: SY
authors.lastname: Shvartsman
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D004330:Drosophila / Q000378:metabolism / Q000502:physiology; D029721:Drosophila Proteins / Q000378:metabolism; D054642:Dual Specificity Phosphatase 6 / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000201:enzymology / Q000378:metabolism; D024002:HMGB Proteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D010766:Phosphorylation; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D049490:Systems Biology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D029721:Drosophila Proteins; D054642:Dual Specificity Phosphatase 6; D024002:HMGB Proteins; D020928:Mitogen-Activated Protein Kinases; D012097:Repressor Proteins; C404284:cic protein, Drosophila; C091023:gro protein, Drosophila