Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tachykinins interact with three neurokinin receptors (NKRs) that are often coexpressed by the same cell. Cellular responses to tachykinins depend on the NKR subtype that is activated. We compared the colocalization of NK1R and NK3R with beta-arrestins 1 and 2, which play major roles in receptor desensitization, endocytosis, and signaling. In cells expressing NK1R, the selective agonist Sar-Met-substance P induced rapid translocation of beta-arrestins 1 and 2 from the cytosol to the plasma membrane and then endosomes, indicative of interaction with both isoforms. In contrast, the NK3R interacted transiently with only beta-arrestin 2 at the plasma membrane. Despite these differences, both NK1R and NK3R similarly desensitized, internalized, and activated MAP kinases. Because interactions with beta-arrestins can explain differences in the rate of receptor resensitization, we compared resensitization of agonist-induced Ca2+ mobilization. The NK1R resensitized greater than twofold more slowly than the NK3R. Replacement of intracellular loop 3 and the COOH tail of the NK1R with comparable domains of the NK3R diminished colocalization of the NK1R with beta-arrestin 1 and accelerated resensitization to that of the NK3R. Thus loop 3 and the COOH tail specify colocalization of the NK1R with beta-arrestin 1 and determine the rate of resensitization.
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PMID:The third intracellular loop and carboxyl tail of neurokinin 1 and 3 receptors determine interactions with beta-arrestins. 1295 28

Cryptococcal meningitis is often associated with elevated IL-10 levels, which suggest a dysregulation in the antifungal immune response. beta-Arrestin 2 plays a major role in desensitization of G-protein-coupled receptors involved in the immune responses, provides a scaffolding platform for modification of many signal transduction proteins, and binds Src and MAP kinases family members. This study compared the levels of beta-arrestin 2 mRNA and protein in peripheral blood mononuclear cells (PBMC) of patients with cryptococcal meningitis detected. The interferon-gamma (IFN-gamma) serum concentration was determined with enzyme-linked immunosorbent assay (ELISA) to reveal its relationship with beta-arrestin 2. The effect of modulation of beta-arrestin 2 on cytotoxic activity against Cryptococcus was explored via transfection and interference of beta-arrestin 2. PBMCs of patients with cryptococcal meningitis exhibited significantly elevated levels of beta-arrestin 2 and a positive correlation between beta-arrestin 2 and IL-10 levels existed in patients' serum, but a negative correlation was found between beta-arrestin 2 and IFN-gamma expression. In conclusion, elevated expression of beta-arrestin 2 in PBMCs of patients with cryptococcal meningitis correlated with a reduced cytotoxic activity against Cryptococcus. This study suggests that reduced beta-arrestin 2 mRNA levels or inhibition of beta-arrestin 2 activity may augment INF-gamma production, and ultimately, the anti-Cryptococcus immune response of infected patients.
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PMID:Overexpression of beta-arrestin 2 in peripheral blood mononuclear cells of patients with cryptococcal meningitis. 2003 20