ArticleArthritis research & therapy2011
Aberrant splicing of the hRasGRP4 transcript and decreased levels of this signaling protein in the peripheral blood mononuclear cells in a subset of patients with rheumatoid arthritis.
Article in Arthritis research & therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 11 citations in OpenAlex.
- Dysregulation of RasGRP1 in rheumatoid arthritis and modulation of RasGRP3 as a biomarker of TNFα inhibitors.Arthritis research & therapy · 2015Trial
- Get Spliced: Uniting Alternative Splicing and Arthritis.International journal of molecular sciences · 2024Review
- Mutated RAS-associating proteins and ERK activation in relapse/refractory diffuse large B cell lymphoma.Scientific reports · 2022Article
- The critical role of RasGRP4 in the growth of diffuse large B cell lymphoma.Cell communication and signaling : CCS · 2019Article
- RasGRP3 limits Toll-like receptor-triggered inflammatory response in macrophages by activating Rap1 small GTPase.Nature communications · 2014Article
- Article
- Ras guanine nucleotide-releasing protein-4 (RasGRP4) involvement in experimental arthritis and colitis.The Journal of biological chemistry · 2012Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionAn unidentified population of peripheral blood mononuclear cells (PBMCs) express Ras guanine nucleotide releasing protein 4 (RasGRP4). The aim of our study was to identify the cells in human blood that express hRasGRP4, and then to determine if hRasGRP4 was altered in any patient with rheumatoid arthritis (RA).
methodsMonocytes and T cells were purified from PBMCs of normal individuals, and were evaluated for their expression of RasGRP4 mRNA/protein. The levels of RasGRP4 transcripts were evaluated in the PBMCs from healthy volunteers and RA patients by real-time quantitative PCR. The nucleotide sequences of RasGRP4 cDNAs were also determined. RasGRP4 protein expression in PBMCs/monocytes was evaluated. Recombinant hRasGRP4 was expressed in mammalian cells.
resultsCirculating CD14+ cells in normal individuals were found to express hRasGRP4. The levels of the hRasGRP4 transcript were significantly higher in the PBMCs of our RA patients relative to healthy individuals. Sequence analysis of hRasGRP4 cDNAs from these PBMCs revealed 10 novel splice variants. Aberrantly spliced hRasGRP4 transcripts were more frequent in the RA patients than in normal individuals. The presence of one of these abnormal splice variants was linked to RA. The levels of hRasGRP4 protein in PBMCs tended to be lower. As expected, the defective transcripts led to altered and/or nonfunctional protein in terms of P44/42 mitogen-activated protein (MAP) kinase activation.
conclusionsThe identification of defective isoforms of hRasGRP4 transcripts in the PBMCs of RA patients raises the possibility that dysregulated expression of hRasGRP4 in developing monocytes plays a pathogenic role in a subset of RA patients.
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