ArticleThe EMBO journal1998
A Nck-Pak1 signaling module is required for T-cell receptor-mediated activation of NFAT, but not of JNK.
Article in The EMBO journal, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
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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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Who cites it
44 citing papers in PubMed, 122 citations in OpenAlex.
- ATF6-mediated GTPase RHOQ promotes liver cancer progression via enhancing aerobic glycolysis through PAK1 phosphorylation.Clinical and translational medicine · 2026Article
- Human T-cell receptor triggering requires inactivation of Lim kinase-1 by Slingshot-1 phosphatase.Communications biology · 2024Article
- Wiskott-Aldrich Syndrome Protein: Roles in Signal Transduction in T Cells.Frontiers in cell and developmental biology · 2021Review
- Sinner or Saint?: Nck Adaptor Proteins in Vascular Biology.Frontiers in cell and developmental biology · 2021Review
- Coordinating Cytoskeleton and Molecular Traffic in T Cell Migration, Activation, and Effector Functions.Frontiers in cell and developmental biology · 2020Review
- Pak1 Kinase Promotes Activated T Cell Trafficking by Regulating the Expression of L-Selectin and CCR7.Frontiers in immunology · 2019Article
- Genome-wide CRISPR screen identifies FAM49B as a key regulator of actin dynamics and T cell activation.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Article
- Induced transcription and stability of CELF2 mRNA drives widespread alternative splicing during T-cell signaling.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- miR-155 Controls Lymphoproliferation in LAT Mutant Mice by Restraining T-Cell Apoptosis via SHIP-1/mTOR and PAK1/FOXO3/BIM Pathways.PloS one · 2015Article
- P21-activated kinase in inflammatory and cardiovascular disease.Cellular signalling · 2014Review
- Article
- Protein kinase C-η controls CTLA-4-mediated regulatory T cell function.Nature immunology · 2014Article
- Non-overlapping functions of Nck1 and Nck2 adaptor proteins in T cell activation.Cell communication and signaling : CCS · 2014Article
- Ras and extracellular signal-regulated kinase signaling in thymocytes and T cells.Trends in immunology · 2013Review
- Article
- LAT-independent Erk activation via Bam32-PLC-γ1-Pak1 complexes: GTPase-independent Pak1 activation.Molecular cell · 2012Article
- Autoinhibitory interaction in the multidomain adaptor protein Nck: possible roles in improving specificity and functional diversity.Biochemistry · 2010Article
- SWAP-70-like adapter of T cells: a novel Lck-regulated guanine nucleotide exchange factor coordinating actin cytoskeleton reorganization and Ca2+ signaling in T cells.Immunological reviews · 2009Review
- Angioinhibitory action of NK4 involves impaired extracellular assembly of fibronectin mediated by perlecan-NK4 association.The Journal of biological chemistry · 2009Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The T-cell antigen receptor (TCR) triggers a signaling cascade initiated by the tyrosine kinase Lck and requiring the proto-oncogene p95(vav). Vav is activated by Lck and can function as a guanine nucleotide exchange factor for the Rho-family GTPases, Rac1 and Cdc42. To investigate the involvement of these GTPases in TCR signaling, we focused on their well characterized effector, Pak1. This serine/threonine kinase is activated by GTP-bound Rac1 or Cdc42. However, its role in mediating downstream signaling events is controversial. We observed rapid, TCR-dependent activation of Pak1 and TCR-inducible association of Pak1 with Nck, which was tyrosine phosphorylated following stimulation. Pak1 activation occurred independently of Ras activation or calcium flux, but was dependent on the Lck tyrosine kinase, and was downstream of Vav and Cdc42. Dominant negative Pak1 or Nck specifically inhibited TCR-mediated activation of the nuclear factor of activated T cells (NFAT) transcription factor. TCR-mediated activation of Erk2 was also inhibited by dominant negative Pak. However, Pak1 activation was neither necessary nor sufficient for TCR-dependent c-Jun N-terminal kinase (JNK) activation. Therefore, Pak1 acts downstream of Vav and is required for activation of Erk2 and NFAT by a JNK-independent pathway. This is the first demonstration of a requirement for Pak to mediate the regulation of gene expression by an extracellular ligand.
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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.