ArticleScience signaling2017
The tyrosine phosphatase SHP-1 promotes T cell adhesion by activating the adaptor protein CrkII in the immunological synapse.
Article in Science signaling, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Mechanisms of T cell activation: Integrating signaling pathways, experimental models, and therapeutic implications.EXCLI journal · 2026Review
- Changing the location of proteins on the cell surface is a promising strategy for modulating T cell functions.Immunology · 2024Review
- Distinct bidirectional regulation of LFA1 and α4β7 by Rap1 and integrin adaptors in T cells under shear flow.Cell reports · 2023Article
- Ablation of SYK Kinase from Expanded Primary Human NK Cells via CRISPR/Cas9 Enhances Cytotoxicity and Cytokine Production.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Crk proteins activate the Rap1 guanine nucleotide exchange factor C3G by segregated adaptor-dependent and -independent mechanisms.Cell communication and signaling : CCS · 2023Article
- Treg-specific deletion of the phosphatase SHP-1 impairs control of inflammationFrontiers in immunology · 2023Article
- The critical role of Rap1-GAPs Rasa3 and Sipa1 in T cells for pulmonary transit and egress from the lymph nodes.Frontiers in immunology · 2023Article
- SHP-1 dephosphorylates histone H2B to facilitate its ubiquitination during transcription.The EMBO journal · 2022Article
- Review
- Immune Checkpoint Receptors Signaling in T Cells.International journal of molecular sciences · 2022Review
- Combination Approaches to Target PD-1 Signaling in Cancer.Frontiers in immunology · 2022Review
- Disc Large Homolog 1 Is Critical for Early T Cell Receptor Micro Cluster Formation and Activation in Human T Cells.Vaccines · 2021Article
- SHP2 Targets ITK Downstream of PD-1 to Inhibit T Cell Function.Inflammation · 2021Article
- The Role of the Cytoskeleton in Regulating the Natural Killer Cell Immune Response in Health and Disease: From Signaling Dynamics to Function.Frontiers in cell and developmental biology · 2021Review
- CrkL is required for donor T cell migration to GvHD target organs.Oncotarget · 2020Article
- β2 Integrins-Multi-Functional Leukocyte Receptors in Health and Disease.International journal of molecular sciences · 2020Review
- Modulation of TCR Signaling by Tyrosine Phosphatases: From Autoimmunity to Immunotherapy.Frontiers in cell and developmental biology · 2020Review
- Genetic diversity affects the nanoscale membrane organization and signaling of natural killer cell receptors.Science signaling · 2019Article
- Regulation of CD4Frontiers in immunology · 2019Review
- Crk adaptor proteins mediate actin-dependent T cell migration and mechanosensing induced by the integrin LFA-1.Science signaling · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The adaptor protein CrkII regulates T cell adhesion by recruiting the guanine nucleotide exchange factor C3G, an activator of Rap1. Subsequently, Rap1 stimulates the integrin LFA-1, which leads to T cell adhesion and interaction with antigen-presenting cells (APCs). The adhesion of T cells to APCs is critical for their proper function and education. The interface between the T cell and the APC is known as the immunological synapse. It is characterized by the specific organization of proteins that can be divided into central supramolecular activation clusters (c-SMACs) and peripheral SMACs (p-SMACs). Through total internal reflection fluorescence (TIRF) microscopy and experiments with supported lipid bilayers, we determined that activated Rap1 was recruited to the immunological synapse and localized to the p-SMAC. C3G and the active (dephosphorylated) form of CrkII also localized to the same compartment. In contrast, inactive (phosphorylated) CrkII was confined to the c-SMAC. Activation of CrkII and its subsequent movement from the c-SMAC to the p-SMAC depended on the phosphatase SHP-1, which acted downstream of the T cell receptor. In the p-SMAC, CrkII recruited C3G, which led to Rap1 activation and LFA-1-mediated adhesion of T cells to APCs. Functionally, SHP-1 was necessary for both the adhesion and migration of T cells. Together, these data highlight a signaling pathway in which SHP-1 acts through CrkII to reshape the pattern of Rap1 activation in the immunological synapse.
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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.