ArticleMolecular biology of the cell2007
The M-Ras-RA-GEF-2-Rap1 pathway mediates tumor necrosis factor-alpha dependent regulation of integrin activation in splenocytes.
Article in Molecular biology of the cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
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- Aberrant expression of MRAS and HEG1 as the biomarkers for osimertinib resistance in LUAD.Discover oncology · 2024Article
- Inflammation-Related Risk Loci in Genome-Wide Association Studies of Coronary Artery Disease.Cells · 2021Review
- Phosphatidic acid-dependent localization and basal de-phosphorylation of RA-GEFs regulate lymphocyte trafficking.BMC biology · 2020Article
- The influence of MRAS gene variants on ischemic stroke and serum lipid levels in Chinese Han population.Medicine · 2019Article
- A RAPGEF6 variant constitutes a major risk factor for laryngeal paralysis in dogs.PLoS genetics · 2019Article
- Single-cell cloning of human T-cell lines reveals clonal variation in cell death responses to chemotherapeutics.Cancer genetics · 2019Article
- MRAS: A Close but Understudied Member of the RAS Family.Cold Spring Harbor perspectives in medicine · 2018Review
- Comprehensive behavioral analysis of mice deficient in Rapgef2 and Rapgef6, a subfamily of guanine nucleotide exchange factors for Rap small GTPases possessing the Ras/Rap-associating domain.Molecular brain · 2018Article
- Deletion of Rapgef6, a candidate schizophrenia susceptibility gene, disrupts amygdala function in mice.Translational psychiatry · 2015Article
- Structural and mechanistic insights into the recruitment of talin by RIAM in integrin signaling.Structure (London, England : 1993) · 2014Article
- MRAS Genetic Variation Is Associated with Atherothrombotic Stroke in the Han Chinese Population.Journal of clinical neurology (Seoul, Korea) · 2013Article
- New susceptibility locus for obesity and dyslipidaemia on chromosome 3q22.3.Human genomics · 2013Article
- Data driven linear algebraic methods for analysis of molecular pathways: application to disease progression in shock/trauma.Journal of biomedical informatics · 2012Article
- Ubiquitination: Added complexity in Ras and Rho family GTPase function.Small GTPases · 2011Article
- BAG3 directly associates with guanine nucleotide exchange factor of Rap1, PDZGEF2, and regulates cell adhesion.Biochemical and biophysical research communications · 2010Article
- Genome-wide association study of coronary artery disease.International journal of hypertension · 2010Article
- Specificity in Ras and Rap signaling.The Journal of biological chemistry · 2009Review
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Rap1 small GTPase has been implicated in regulation of integrin-mediated leukocyte adhesion downstream of various chemokines and cytokines in many aspects of inflammatory and immune responses. However, the mechanism for Rap1 regulation in the adhesion signaling remains unclear. RA-GEF-2 is a member of the multiple-member family of guanine nucleotide exchange factors (GEFs) for Rap1 and characterized by the possession of a Ras/Rap1-associating domain, interacting with M-Ras-GTP as an effector, in addition to the GEF catalytic domain. Here, we show that RA-GEF-2 is specifically responsible for the activation of Rap1 that mediates tumor necrosis factor-alpha (TNF-alpha)-triggered integrin activation. In BAF3 hematopoietic cells, activated M-Ras potently induced lymphocyte function-associated antigen 1 (LFA-1)-mediated cell aggregation. This activation was totally abrogated by knockdown of RA-GEF-2 or Rap1. TNF-alpha treatment activated LFA-1 in a manner dependent on M-Ras, RA-GEF-2, and Rap1 and induced activation of M-Ras and Rap1 in the plasma membrane, which was accompanied by recruitment of RA-GEF-2. Finally, we demonstrated that M-Ras and RA-GEF-2 were indeed involved in TNF-alpha-stimulated and Rap1-mediated LFA-1 activation in splenocytes by using mice deficient in RA-GEF-2. These findings proved a crucial role of the cross-talk between two Ras-family GTPases M-Ras and Rap1, mediated by RA-GEF-2, in adhesion signaling.
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