ArticleMolecular biology of the cell2003
The critical cytoplasmic regions of the alphaL/beta2 integrin in Rap1-induced adhesion and migration.
Article in Molecular biology of the cell, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 103 citations in OpenAlex.
- Tumor cells escape immunosurveillance by hampering LFA-1.Frontiers in immunology · 2025Review
- CD56/NCAM mediates cell migration of human NK cells by promoting integrin-mediated adhesion turnover.Molecular biology of the cell · 2024Article
- CD56/NCAM mediates cell migration of human NK cells by promoting integrin-mediated adhesion turnover.bioRxiv : the preprint server for biology · 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
- Article
- Phagocytic Integrins: Activation and Signaling.Frontiers in immunology · 2020Review
- Rap1 regulates hepatic stellate cell migration through the modulation of RhoA activity in response to TGF‑β1.International journal of molecular medicine · 2019Article
- Aggregatibacter actinomycetemcomitans leukotoxin causes activation of lymphocyte function-associated antigen 1.Cellular microbiology · 2019Article
- Actionable Activating Oncogenic ERBB2/HER2 Transmembrane and Juxtamembrane Domain Mutations.Cancer cell · 2018Article
- The membrane-distal regions of integrin α cytoplasmic domains contribute differently to integrin inside-out activation.Scientific reports · 2018Article
- LFA-1 in T Cell Migration and Differentiation.Frontiers in immunology · 2018Review
- Dynamin2 controls Rap1 activation and integrin clustering in human T lymphocyte adhesion.PloS one · 2017Article
- Leukocyte arrest: Biomechanics and molecular mechanisms of β2 integrin activation.Biorheology · 2015Review
- WASH knockout T cells demonstrate defective receptor trafficking, proliferation, and effector function.Molecular and cellular biology · 2013Article
- Ezrin and moesin are required for efficient T cell adhesion and homing to lymphoid organs.PloS one · 2013Article
- Radil controls neutrophil adhesion and motility through β2-integrin activation.Molecular biology of the cell · 2012Article
- The Gαq/11 proteins contribute to T lymphocyte migration by promoting turnover of integrin LFA-1 through recycling.PloS one · 2012Article
- T cell receptor "inside-out" pathway via signaling module SKAP1-RapL regulates T cell motility and interactions in lymph nodes.Immunity · 2010Article
- The final steps of integrin activation: the end game.Nature reviews. Molecular cell biology · 2010Review
- Identifying the rules of engagement enabling leukocyte rolling, activation, and adhesion.PLoS computational biology · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rap1 is a potent inside-out signal that increases LFA-1 adhesive activity. In this study, we have defined the cytoplasmic region of the alphaL and beta2 integrin that are required for Rap1-stimulated adhesion and subsequent migration on ICAM-1. Human LFA-1 bearing truncated and point-mutated alphaL and beta2 cytoplasmic regions were reconstituted in mouse IL-3-dependent proB cells, BAF/3. Truncation of the alphaL, but not beta2 subunit cytoplasmic region, abolished Rap1V12-dependent adhesion to ICAM-1. The alanine substitution of two lysine residues (K1097/K1099) in the alphaL subunit was found to be critical in adhesion induced by Rap1V12, but not PMA. This mutation suppressed Rap1V12-induced LFA-1 conformation changes and ligand-binding affinity. The K1097/K1099 mutation also impaired binding to ICAM-1 induced by TCR cross-linking or SDF-1. In contrast, the alanine substitution for tyrosine in the beta2 subunit endocytosis motif inhibited internalization of LFA-1, and severely impaired detachment at the cell rear, which resulted in long-elongated cell shapes. This result demonstrates that internalization of LFA-1 is a critical step in the deadhesion process. Our study revealed novel requirements of amino acid residues of the LFA-1 cytoplasmic region in the response to the inside-out signaling and the subsequent deadhesion process.
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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.