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Literature summary for 3.6.5.2 extracted from

  • Carvalho, B.C.; Oliveira, L.C.; Rocha, C.D.; Fernandes, H.B.; Oliveira, I.M.; Leao, F.B.; Valverde, T.M.; Rego, I.M.G.; Ghosh, S.; Silva, A.M.
    Both knock-down and overexpression of Rap2a small GTPase in macrophages result in impairment of NF-kappaB activity and inflammatory gene expression (2019), Mol. Immunol., 109, 27-37 .
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
lipopolysaccharide Rap2a is activated by lipopolysaccharide in macrophages. In contrast to mRNA levels, Rap2a protein levels are increased after lipopolysaccharide treatments of macrophages Mus musculus
additional information putative activator TLR-inducible Ras guanine exchange factor RasGEF1b is sufficient to induce, it is not fully required for Rap2a activation Mus musculus

Cloned(Commentary)

Cloned (Comment) Organism
quantitative RT-PCR enzyme expression analysis, cotransfection of the NF-kappaB reporter with TLR2, TLR3, and TLR4, CD14, MD2 and Rap2a encoding plasmids into HEK-293 cells, and further treating the cells with the TLR ligands Mus musculus

Protein Variants

Protein Variants Comment Organism
additional information knockdown and overexpression of Rap2a small GTPase in macrophages resulting in impairment of NF-kappaB activity and inflammatory gene expression Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
GTP + H2O Mus musculus
-
GDP + phosphate
-
?

Organism

Organism UniProt Comment Textmining
Mus musculus Q80ZJ1
-
-

Source Tissue

Source Tissue Comment Organism Textmining
bone marrow-derived macrophage
-
Mus musculus
-
macrophage TLRs agonists induce changes in the expression of Rap2a in macrophages. In contrast to mRNA levels, Rap2a protein levels are increased after LPS treatments of macrophages Mus musculus
-
RAW-264.7 cell
-
Mus musculus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
GTP + H2O
-
Mus musculus GDP + phosphate
-
?

Synonyms

Synonyms Comment Organism
Rap2a
-
Mus musculus
small GTPase
-
Mus musculus

Expression

Organism Comment Expression
Mus musculus expression levels of Rap2a in macrophages might be tightly regulated to avoid unbalanced immune response additional information
Mus musculus putative activator TLR-inducible Ras guanine exchange factor RasGEF1b is sufficient to induce, it is not fully required for Rap2a activation. In contrast to mRNA levels, Rap2a protein levels are increased after lipopolysaccharide treatments of macrophages up

General Information

General Information Comment Organism
evolution the subfamily of Ras-like small GTPases contains numerous members including classical Ras (H-, K-, and N-Ras), R-Ras, TC21/R-Ras2, MRas/R-Ras3, DexRas1/RasD1, RalA/B, Rheb, Rit, Rin, Rap1 and Rap2, and atypical kappaB-Ras1 and kappaB-Ras2 Mus musculus
malfunction both knockdown and overexpression of Rap2a small GTPase in macrophages result in impairment of NF-kappaB activity and inflammatory gene expression. Silencing of Rap2a impairs LPS-induced production of IL-6 cytokine and KC/Cxcl1 chemokine, and also NF-kappaB activity. Overexpression of Rap2a does also lead to marked inhibition of NF-kappaB activation induced by LPS, Pam3CSK4, and downstream TLR signaling molecules. Dysregulation of Rap2a expression in an inflammatory context may significantly alter the status of NF-kappaB activation Mus musculus
metabolism Rap2a is activated by lipopolysaccharide in macrophages, and although putative activator TLR-inducible Ras guanine exchange factor RasGEF1b is sufficient to induce, it is not fully required for Rap2a activation. Dysregulation of Rap2a expression in an inflammatory context may significantly alter the status of NF-kappaB activation Mus musculus
physiological function small Ras GTPases are key molecules that regulate a variety of cellular responses in different cell types. Rap2a. Rap2a can inhibit the LPS-induced phosphorylation of the NF-kappaB subunit p65 at serine 536. Rap2a is implicated in TLR-mediated responses by contributing to balanced NF-kappaB activity status in macrophages. Rap2a GTPase is involved in TLR signaling pathway to NF-kappaB. Rap2a exhibits a more potent inhibitory effect on Mal/TIRAP and TRAF6-induced NF-kappaB activation. In contrast, Rap2a fails to inhibit NF-kappaB activity induced directly by the monomer p65(RelA). Thus, Rap2a interferes in NF-kappaB activation by affecting upstream signaling events to p65(RelA) Mus musculus