ArticleThe Journal of cell biology2019
A kindlin-3-leupaxin-paxillin signaling pathway regulates podosome stability.
Article in The Journal of cell biology, 2019. 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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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
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- A flexible loop in the paxillin LIM3 domain mediates its direct binding to integrin β subunits.PLoS biology · 2024Article
- Transcriptome Analyses of Liver Sinusoidal Endothelial Cells Reveal a Consistent List of Candidate Genes Associated with Endothelial Dysfunction and the Fibrosis Progression.Current issues in molecular biology · 2024Article
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- Integrin Regulators in Neutrophils.Cells · 2022Review
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- Humanized β2 Integrin-Expressing Hoxb8 Cells Serve as Model to Study Integrin Activation.Cells · 2022Article
- Mechanism of integrin activation by talin and its cooperation with kindlin.Nature communications · 2022Article
- Integrin-Mediated Tumorigenesis and Its Therapeutic Applications.Frontiers in oncology · 2022Review
- Paxillin binding to the PH domain of kindlin-3 in platelets is required to support integrin αIIbβ3 outside-in signaling.Journal of thrombosis and haemostasis : JTH · 2021Article
- Initiation of focal adhesion assembly by talin and kindlin: A dynamic view.Protein science : a publication of the Protein Society · 2021Review
- Differences in self-association between kindlin-2 and kindlin-3 are associated with differential integrin binding.The Journal of biological chemistry · 2020Article
- Chapter 22: Structural and signaling functions of integrins.Biochimica et biophysica acta. Biomembranes · 2020Review
- Conformationally active integrin endocytosis and traffic: why, where, when and how?Biochemical Society transactions · 2020Review
- Review
- Kindlin-3 stokes the life span of podosomes.The Journal of cell biology · 2019Article
- Site-specific phosphorylation regulates the functions of kindlin-3 in a variety of cells.Life science alliance · 2019Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Binding of kindlins to integrins is required for integrin activation, stable ligand binding, and subsequent intracellular signaling. How hematopoietic kindlin-3 contributes to the assembly and stability of the adhesion complex is not known. Here we report that kindlin-3 recruits leupaxin into podosomes and thereby regulates paxillin phosphorylation and podosome turnover. We demonstrate that the activity of the protein tyrosine phosphatase PTP-PEST, which controls paxillin phosphorylation, requires leupaxin. In contrast, despite sharing the same binding mode with leupaxin, paxillin recruitment into podosomes is kindlin-3 independent. Instead, we found paxillin together with talin and vinculin in initial adhesion patches of kindlin-3-null cells. Surprisingly, despite its presence in these early adhesion patches, podosomes can form in the absence of paxillin or any paxillin member. In conclusion, our findings show that kindlin-3 not only activates and clusters integrins into podosomes but also regulates their lifetime by recruiting leupaxin, which controls PTP-PEST activity and thereby paxillin phosphorylation and downstream signaling.
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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.