ArticleThe Journal of clinical investigation2015
CRK proteins selectively regulate T cell migration into inflamed tissues.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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The trial behind it
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
42 citing papers in PubMed, 67 citations in OpenAlex.
- A phase 2a double-blind, placebo-controlled, randomized clinical trial evaluating the efficacy and safety of NuGel, a novel topical GPCR19-mediated inflammasome inhibitor, in patients with mild to moderate atopic dermatitis: a proof-of-concept study withFrontiers in immunology · 2025Trial
- Development of Antagonist Peptides of the Crk/CrkL SH2 Domains by Modifying the Peripheral Amino Acid Residues of the YXXP Motif.Biochemistry · 2026Article
- β-Catenin stabilization protects against alveolar hemorrhage through amphiregulin- and BATF-mediated Tregs.JCI insight · 2026Article
- Article
- The scaffold protein CasL restrains membrane blebbing and promotes T cell migration.Journal of cell science · 2025Article
- The p130Cas-Crk/CrkL Axis: A Therapeutic Target for Invasive Cancers Unveiled by Collaboration Among p130Cas, Crk, and CrkL.International journal of molecular sciences · 2025Review
- SLAMF7 (CD319) on activated CD8Cell death and differentiation · 2025Article
- Comprehensive transcriptome, miRNA and kinome profiling identifies new treatment options for personalized lung cancer therapy.Clinical and translational medicine · 2025Article
- Integrated Computational Analysis Reveals Early Genetic and Epigenetic AML Susceptibility Biomarkers in Benzene-Exposed Workers.International journal of molecular sciences · 2025Article
- Plasma proteomics in children with new-onset type 1 diabetes identifies new potential biomarkers of partial remission.Scientific reports · 2024Article
- Microengineered In Vitro Assays for Screening and Sorting Manufactured Therapeutic T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2024Review
- Comprehensive time-course gene expression evaluation of high-risk beef cattle to establish immunological characteristics associated with undifferentiated bovine respiratory disease.Frontiers in immunology · 2024Article
- Crk proteins activate the Rap1 guanine nucleotide exchange factor C3G by segregated adaptor-dependent and -independent mechanisms.Cell communication and signaling : CCS · 2023Article
- Time-resolved RNA signatures of CD4+ T cells in Parkinson's disease.Cell death discovery · 2023Article
- Specific targeting of glioblastoma with an oncolytic virus expressing a cetuximab-CCL5 fusion protein via innate and adaptive immunity.Nature cancer · 2022Article
- Control of CRK-RAC1 activity by the miR-1/206/133 miRNA family is essential for neuromuscular junction function.Nature communications · 2022Article
- Phosphorylation of CrkL S114 induced by common gamma chain cytokines and T-cell receptor signal transduction.Scientific reports · 2021Article
- Review
- Natural Killer Cell Integrins and Their Functions in Tissue Residency.Frontiers in immunology · 2021Review
- The Transmembrane Adaptor Protein LIME Is Essential for Chemokine-Mediated Migration of Effector T Cells to Inflammatiory Sites.Molecules and cells · 2020Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Effector T cell migration into inflamed sites greatly exacerbates tissue destruction and disease severity in inflammatory diseases, including graft-versus-host disease (GVHD). T cell migration into such sites depends heavily on regulated adhesion and migration, but the signaling pathways that coordinate these functions downstream of chemokine receptors are largely unknown. Using conditional knockout mice, we found that T cells lacking the adaptor proteins CRK and CRK-like (CRKL) exhibit reduced integrin-dependent adhesion, chemotaxis, and diapedesis. Moreover, these two closely related proteins exhibited substantial functional redundancy, as ectopic expression of either protein rescued defects in T cells lacking both CRK and CRKL. We determined that CRK proteins coordinate with the RAP guanine nucleotide exchange factor C3G and the adhesion docking molecule CASL to activate the integrin regulatory GTPase RAP1. CRK proteins were required for effector T cell trafficking into sites of inflammation, but not for migration to lymphoid organs. In a murine bone marrow transplantation model, the differential migration of CRK/CRKL-deficient T cells resulted in efficient graft-versus-leukemia responses with minimal GVHD. Together, the results from our studies show that CRK family proteins selectively regulate T cell adhesion and migration at effector sites and suggest that these proteins have potential as therapeutic targets for preventing GVHD.
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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.