ArticleThe Journal of biological chemistry2011
The adaptor-associated kinase 1, AAK1, is a positive regulator of the Notch pathway.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 53 citations in OpenAlex.
- Exploring the AAK1 Phospho-signaling Landscape Through Phospho-centric Co-regulation Network.Cell biochemistry and biophysics · 2026Article
- Intrinsic dysfunction in muscle stem cells lacking dystrophin begins during secondary myogenesis.Nature communications · 2025Article
- Article
- Comprehensive analysis based on glycolytic and glutaminolytic pathways signature for predicting prognosis and immunotherapy in ovarian cancer.Journal of Cancer · 2024Article
- Recent progress in discovery of novel AAK1 inhibitors: from pain therapy to potential anti-viral agents.Journal of enzyme inhibition and medicinal chemistry · 2023Review
- Phosphorylation of ADAPTOR PROTEIN-2 μ-adaptin by ADAPTOR-ASSOCIATED KINASE1 regulates the tropic growth of Arabidopsis roots.The Plant cell · 2023Article
- Current thoughts on cellular functions of numb-associated kinases.Molecular biology reports · 2023Review
- Multiplexed kinase interactome profiling quantifies cellular network activity and plasticity.Molecular cell · 2023Article
- Adaptor protein complex interaction map in Arabidopsis identifies P34 as a common stability regulator.Nature plants · 2023Article
- TNIK signaling imprints CD8Nature communications · 2020Article
- SGC-AAK1-1: A Chemical Probe Targeting AAK1 and BMP2K.ACS medicinal chemistry letters · 2020Article
- Serine/Threonine Protein Kinase STK16.International journal of molecular sciences · 2019Review
- WNT Activates the AAK1 Kinase to Promote Clathrin-Mediated Endocytosis of LRP6 and Establish a Negative Feedback Loop.Cell reports · 2019Article
- Chemical genetic identification of GAK substrates reveals its role in regulating NaLife science alliance · 2018Article
- Viral journeys on the intracellular highways.Cellular and molecular life sciences : CMLS · 2018Review
- Ndr kinases regulate retinal interneuron proliferation and homeostasis.Scientific reports · 2018Article
- The autophagy machinery restrains iNKT cell activation through CD1D1 internalization.Autophagy · 2017Article
- Plasma miR-324-3p and miR-1285 as diagnostic and prognostic biomarkers for early stage lung squamous cell carcinoma.Oncotarget · 2016Article
- Inhibition of AAK1 Kinase as a Novel Therapeutic Approach to Treat Neuropathic Pain.The Journal of pharmacology and experimental therapeutics · 2016Article
- Immune signatures and disorder-specific patterns in a cross-disorder gene expression analysis.The British journal of psychiatry : the journal of mental science · 2016Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Notch pathway is involved in cell-cell signaling during development and adulthood from invertebrates to higher eukaryotes. Activation of the Notch receptor by its ligands relies upon a multi-step processing. The extracellular part of the receptor is removed by a metalloprotease of the ADAM family and the remaining fragment is cleaved within its transmembrane domain by a presenilin-dependent γ-secretase activity. γ-Secretase processing of Notch has been shown to depend upon monoubiquitination as well as clathrin-mediated endocytosis (CME). We show here that AAK1, the adaptor-associated kinase 1, directly interacts with the membrane-tethered active form of Notch released by metalloprotease cleavage. Active AAK1 acts upstream of the γ-secretase cleavage by stabilizing both the membrane-tethered activated form of Notch and its monoubiquitinated counterpart. We propose that AAK1 acts as an adaptor for Notch interaction with components of the clathrin-mediated pathway such as Eps15b. Moreover, transfected AAK1 increases the localization of activated Notch to Rab5-positive endocytic vesicles, while AAK1 depletion or overexpression of Numb, an inhibitor of the pathway, interferes with this localization. These results suggest that after ligand-induced activation of Notch, the membrane-tethered form can be directed to different endocytic pathways leading to distinct fates.
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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.