ArticleMolecular systems biology2015
Systematic discovery of linear binding motifs targeting an ancient protein interaction surface on MAP kinases.
Article in Molecular systems biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 67 citations in OpenAlex.
- TrxR1 inhibition sensitizes hepatocellular carcinoma to Motesanib via an autophagy-ROS-JNK/ER stress axis.Biology direct · 2026Article
- Evolutionary analysis through structural modeling of FAM222 proteins reveals a novel disordered conserved domain in vertebrates that interacts with NLK.Scientific reports · 2025Article
- Bipartite binding of the intrinsically disordered scaffold protein JIP1 to the kinase JNK1.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Reversible covalent c-Jun N-terminal kinase inhibitors targeting a specific cysteine by precision-guided Michael-acceptor warheads.Nature communications · 2024Article
- Targeting a key protein-protein interaction surface on mitogen-activated protein kinases by a precision-guided warhead scaffold.Nature communications · 2024Article
- Determining the ERK-regulated phosphoproteome driving KRAS-mutant cancer.Science (New York, N.Y.) · 2024Article
- Discovery and Characterization of Linear Motif Mediated Protein-Protein Complexes.Advances in experimental medicine and biology · 2024Article
- Linear motif specificity in signaling through p38α and ERK2 mitogen-activated protein kinases.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Hydrogen peroxide-dependent oxidation of ERK2 within its D-recruitment site alters its substrate selection.iScience · 2023Article
- Navigating the ERK1/2 MAPK Cascade.Biomolecules · 2023Review
- Phosphorylation-Assisted Luciferase Complementation Assay Designed to Monitor Kinase Activity and Kinase-Domain-Mediated Protein-Protein Binding.International journal of molecular sciences · 2023Article
- Architecture of the MKK6-p38α complex defines the basis of MAPK specificity and activation.Science (New York, N.Y.) · 2023Article
- JNK Cascade-Induced Apoptosis-A Unique Role in GqPCR Signaling.International journal of molecular sciences · 2023Review
- Proteome-wide screening for mitogen-activated protein kinase docking motifs and interactors.Science signaling · 2023Article
- ERK2 MAP kinase regulates SUFU binding by multisite phosphorylation of GLI1.Life science alliance · 2022Article
- Substrates of the MAPK Slt2: Shaping Yeast Cell Integrity.Journal of fungi (Basel, Switzerland) · 2022Review
- Systematic Discovery of FBXW7-Binding Phosphodegrons Highlights Mitogen-Activated Protein Kinases as Important Regulators of Intracellular Protein Levels.International journal of molecular sciences · 2022Article
- A non-catalytic herpesviral protein reconfigures ERK-RSK signaling by targeting kinase docking systems in the host.Nature communications · 2022Article
- Orchestrating serine/threonine phosphorylation and elucidating downstream effects by short linear motifs.The Biochemical journal · 2022Review
- A walk-through MAPK structure and functionality with the 30-year-old yeast MAPK Slt2.International microbiology : the official journal of the Spanish Society for Microbiology · 2021Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitogen-activated protein kinases (MAPK) are broadly used regulators of cellular signaling. However, how these enzymes can be involved in such a broad spectrum of physiological functions is not understood. Systematic discovery of MAPK networks both experimentally and in silico has been hindered because MAPKs bind to other proteins with low affinity and mostly in less-characterized disordered regions. We used a structurally consistent model on kinase-docking motif interactions to facilitate the discovery of short functional sites in the structurally flexible and functionally under-explored part of the human proteome and applied experimental tools specifically tailored to detect low-affinity protein-protein interactions for their validation in vitro and in cell-based assays. The combined computational and experimental approach enabled the identification of many novel MAPK-docking motifs that were elusive for other large-scale protein-protein interaction screens. The analysis produced an extensive list of independently evolved linear binding motifs from a functionally diverse set of proteins. These all target, with characteristic binding specificity, an ancient protein interaction surface on evolutionarily related but physiologically clearly distinct three MAPKs (JNK, ERK, and p38). This inventory of human protein kinase binding sites was compared with that of other organisms to examine how kinase-mediated partnerships evolved over time. The analysis suggests that most human MAPK-binding motifs are surprisingly new evolutionarily inventions and newly found links highlight (previously hidden) roles of MAPKs. We propose that short MAPK-binding stretches are created in disordered protein segments through a variety of ways and they represent a major resource for ancient signaling enzymes to acquire new regulatory roles.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.