ArticleThe Biochemical journal2017
Molecular determinants of KA1 domain-mediated autoinhibition and phospholipid activation of MARK1 kinase.
Article in The Biochemical journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Cell cycle oscillations in a polarity network facilitate state switching by morphogenetic cues.Science advances · 2026Article
- The role of MELK in cancer: mechanisms and therapeutic options.Frontiers in oncology · 2026Review
- Proximity labeling of DAF-16 FOXO highlights aging regulatory proteins.Nature communications · 2025Article
- Cell cycle oscillations in a polarity network facilitate state switching by morphogenetic cues.bioRxiv : the preprint server for biology · 2025Article
- Mechanisms of growth-dependent regulation of the Gin4 kinase.Molecular biology of the cell · 2025Article
- Mechanisms of growth-dependent regulation of the Gin4 kinase.bioRxiv : the preprint server for biology · 2024Article
- Spatiotemporal regulation of MELK during mitosis.Frontiers in cell and developmental biology · 2024Article
- Computational analysis of regulatory regions in human protein kinases.Protein science : a publication of the Protein Society · 2023Article
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- Kinase Activity of PAR1b, Which Mediates Nuclear Translocation of the BRCA1 Tumor Suppressor, Is Potentiated by Nucleic Acid-Mediated PAR1b Multimerization.International journal of molecular sciences · 2022Article
- Growth-Dependent Activation of Protein Kinases Suggests a Mechanism for Measuring Cell Growth.Genetics · 2020Article
- Long Noncoding RNA (lncRNA) MT1JP Suppresses Hepatocellular Carcinoma (HCC) in vitro.Cancer management and research · 2020Article
- Spatial regulation of the polarity kinase PAR-1 by parallel inhibitory mechanisms.Development (Cambridge, England) · 2019Article
- Article
- Polyphosphoinositide-Binding Domains: Insights from Peripheral Membrane and Lipid-Transfer Proteins.Advances in experimental medicine and biology · 2019Review
- Chk1 KA1 domain auto-phosphorylation stimulates biological activity and is linked to rapid proteasomal degradation.Scientific reports · 2018Article
- Structural Basis for MARK1 Kinase Autoinhibition by Its KA1 Domain.Structure (London, England : 1993) · 2018Article
- Intramolecular autoinhibition of checkpoint kinase 1 is mediated by conserved basic motifs of the C-terminal kinase-associated 1 domain.The Journal of biological chemistry · 2017Article
- Flipping states: a few key residues decide the winning conformation of the only universally conserved transcription factor.Nucleic acids research · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Protein kinases are frequently regulated by intramolecular autoinhibitory interactions between protein modules that are reversed when these modules bind other 'activating' protein or membrane-bound targets. One group of kinases, the MAP/microtubule affinity-regulating kinases (MARKs) contain a poorly understood regulatory module, the KA1 (kinase associated-1) domain, at their C-terminus. KA1 domains from MARK1 and several related kinases from yeast to humans have been shown to bind membranes containing anionic phospholipids, and peptide ligands have also been reported. Deleting or mutating the C-terminal KA1 domain has been reported to activate the kinase in which it is found - also suggesting an intramolecular autoinhibitory role. Here, we show that the KA1 domain of human MARK1 interacts with, and inhibits, the MARK1 kinase domain. Using site-directed mutagenesis, we identify residues in the KA1 domain required for this autoinhibitory activity, and find that residues involved in autoinhibition and in anionic phospholipid binding are the same. We also demonstrate that a 'mini' MARK1 becomes activated upon association with vesicles containing anionic phospholipids, but only if the protein is targeted to these vesicles by a second signal. These studies provide a mechanistic basis for understanding how MARK1 and its relatives may require more than one signal at the membrane surface to control their activation at the correct location and time. MARK family kinases have been implicated in a plethora of disease states including Alzheimer's, cancer, and autism, so advancing our understanding of their regulatory mechanisms may ultimately have therapeutic value.
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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 OpenQuestion graph.