ArticleThe Journal of biological chemistry2020
Small molecule AX-024 reduces T cell proliferation independently of CD3ϵ/Nck1 interaction, which is governed by a domain swap in the Nck1-SH3.1 domain.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- Implicates of PIP5K1α in asthma-related biological processes: insights into mechanisms and therapeutic potential.Journal of translational medicine · 2025Review
- Understanding domain swapping in the c-Src SH3 domain through hinge-loop mutagenesis.Acta crystallographica. Section D, Structural biology · 2025Article
- Targeting of microvillus protein Eps8 by the NleH effector kinases from enteropathogenicProceedings of the National Academy of Sciences of the United States of America · 2022Article
- New Label-Free Biosensing for the Evaluation of the AX-024 Inhibitor: Case Study for the Development of New Drugs in Autoimmune Diseases.Sensors (Basel, Switzerland) · 2022Article
- Nck adaptors at a glance.Journal of cell science · 2021Article
- The impact of oncogenic mutations of the viral Src kinase on the structure and stability of the SH3 domain.Acta crystallographica. Section D, Structural biology · 2021Article
- Sinner or Saint?: Nck Adaptor Proteins in Vascular Biology.Frontiers in cell and developmental biology · 2021Review
- Reply to Alarcon and Borroto: Small molecule AX-024 reduces T cell proliferation independently of CD3ε-Nck1 interaction at SH3.1.The Journal of biological chemistry · 2020Article
- Small molecule AX-024 targets T cell receptor signaling by disrupting CD3ε-Nck interaction.The Journal of biological chemistry · 2020Article
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13 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Activation of the T cell receptor (TCR) results in binding of the adapter protein Nck (noncatalytic region of tyrosine kinase) to the CD3ϵ subunit of the TCR. The interaction was suggested to be important for the amplification of TCR signals and is governed by a proline-rich sequence (PRS) in CD3ϵ that binds to the first Src homology 3 (SH3) domain of Nck (Nck-SH3.1). Inhibition of this protein/protein interaction ameliorated inflammatory symptoms in mouse models of multiple sclerosis, psoriasis, and asthma. A small molecule, AX-024, was reported to inhibit the Nck/CD3ϵ interaction by physically binding to the Nck1-SH3.1 domain, suggesting a route to develop an inhibitor of the Nck1/CD3ϵ interaction for modulating TCR activity in autoimmune and inflammatory diseases. We show here that AX-024 reduces T cell proliferation upon weak TCR stimulation but does not significantly affect phosphorylation of Zap70 (ζ chain of T cell receptor-associated protein kinase 70). We also find that AX-024 is likely not involved in modulating the Nck/TCR interaction but probably has other targets in T cells. An array of biophysical techniques did not detect a direct interaction between AX-024 and Nck-SH3.1
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