ArticleChemistry & biology2011
AAK1 identified as an inhibitor of neuregulin-1/ErbB4-dependent neurotrophic factor signaling using integrative chemical genomics and proteomics.
Article in Chemistry & biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 39 citations in OpenAlex.
- Development of pyrazolo[1,5-a]pyrimidine based macrocyclic kinase inhibitors targeting AAK1.European journal of medicinal chemistry · 2025Article
- Development of a novel AAK1 inhibitor via Kinobeads-based screening.Scientific reports · 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
- Phospho-PTM proteomic discovery of novel EPO- modulated kinases and phosphatases, including PTPN18 as a positive regulator of EPOR/JAK2 Signaling.Cellular signalling · 2020Article
- Genome-wide profiling of DNA methylome and transcriptome in peripheral blood monocytes for major depression: A Monozygotic Discordant Twin Study.Translational psychiatry · 2019Article
- Synthesis and Structure-Activity Relationships of 3,5-Disubstituted-pyrrolo[2,3- b]pyridines as Inhibitors of Adaptor-Associated Kinase 1 with Antiviral Activity.Journal of medicinal chemistry · 2019Article
- 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
- Inhibitors of Adaptor-Associated Kinase 1 (AAK1) May Treat Neuropathic Pain, Schizophrenia, Parkinson's Disease, and Other Disorders.ACS medicinal chemistry letters · 2017Article
- Inhibition of AAK1 Kinase as a Novel Therapeutic Approach to Treat Neuropathic Pain.The Journal of pharmacology and experimental therapeutics · 2016Article
- Family-wide Structural Analysis of Human Numb-Associated Protein Kinases.Structure (London, England : 1993) · 2016Article
- Interneuronal DISC1 regulates NRG1-ErbB4 signalling and excitatory-inhibitory synapse formation in the mature cortex.Nature communications · 2015Article
- Rapid profiling of protein kinase inhibitors by quantitative proteomics.MedChemComm · 2014Article
- Target identification and mechanism of action in chemical biology and drug discovery.Nature chemical biology · 2013Review
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
Target identification remains challenging for the field of chemical biology. We describe an integrative chemical genomic and proteomic approach combining the use of differentially active analogs of small molecule probes with stable isotope labeling by amino acids in cell culture-mediated affinity enrichment, followed by subsequent testing of candidate targets using RNA interference-mediated gene silencing. We applied this approach to characterizing the natural product K252a and its ability to potentiate neuregulin-1 (Nrg1)/ErbB4 (v-erb-a erythroblastic leukemia viral oncogene homolog 4)-dependent neurotrophic factor signaling and neuritogenesis. We show that AAK1 (adaptor-associated kinase 1) is a relevant target of K252a, and that the loss of AAK1 alters ErbB4 trafficking and expression levels, providing evidence for a previously unrecognized role for AAK1 in Nrg1-mediated neurotrophic factor signaling. Similar strategies should lead to the discovery of novel targets for therapeutic development.
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Registered trials
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.