Gene regulation by MAPK substrate competition. Author Yoosik Kim, María Andreu, Bomyi Lim, Kwanghun Chung, Mark Terayama, Gerardo Jiménez, Celeste Berg, Hang Lu, Stanislav Shvartsman Publication Year 2011 Type Journal Article Abstract Developing tissues are patterned by coordinated activities of signaling systems, which can be integrated by a regulatory region of a gene that binds multiple transcription factors or by a transcription factor that is modified by multiple enzymes. Based on a combination of genetic and imaging experiments in the early Drosophila embryo, we describe a signal integration mechanism that cannot be reduced to a single gene regulatory element or a single transcription factor. This mechanism relies on an enzymatic network formed by mitogen-activated protein kinase (MAPK) and its substrates. Specifically, anteriorly localized MAPK substrates, such as Bicoid, antagonize MAPK-dependent downregulation of Capicua, a repressor that is involved in gene regulation along the dorsoventral axis of the embryo. MAPK substrate competition provides a basis for ternary interaction of the anterior, dorsoventral, and terminal patterning systems. A mathematical model of this interaction can explain gene expression patterns with both anteroposterior and dorsoventral polarities. Keywords Animals, Drosophila Proteins, Gene Expression Regulation, Developmental, Signal Transduction, Embryo, Nonmammalian, Female, In Situ Hybridization, Drosophila melanogaster, Trans-Activators, Models, Theoretical, Repressor Proteins, Homeodomain Proteins, HMGB Proteins, Immunoenzyme Techniques, Phosphorylation, Mitogen-Activated Protein Kinases Journal Dev Cell Volume 20 Issue 6 Pages 880-7 Date Published 06/2011 Alternate Journal Dev. Cell Google ScholarBibTeXEndNote X3 XML