Formyl peptide receptor activation

While none of these neutrophil receptors has yet been sequenced, partial purification of the formyl peptide receptors has been reported (16). The formyl peptide receptor is particularly attractive because of the extensive structure-activity studies on peptide ligands by Freer and coworkers (17,18). The receptor is a trans-membrane glycoprotein with apparent molecular weight of 60,000 based on proteolysis (19) and photoaffinity (20) labeling studies. 

Shen W, Li B, Wetzel MA, Rogers TJ, Henderson EE, Su SB, Gong W, Le Y, Sargeant R, Dimitrov DS, Oppenheim JJ, Wang JM (2000) Down-regulation of the chemokine receptor CCR5 by activation of chemotactic formyl peptide receptor in human monocytes. Blood 96 2887-2894... 

Ernst, S., Lange. C., Wilbers, A., Goebeler, V., Gerke, V., and U. Rescher, 2004, An annexin 1 N-terminal peptide activates leukocytes by triggering different members of die formyl peptide receptor family. J Immunol. 172(12) 7669-76. 

Gripentrog, J. M., Jesaitis, A. J., and Miettinen, H. M. (2000). A single amino acid substitution (N297A) in the conserved NPXXY sequence of the human N-formyl peptide receptor results in inhibition of desensitization and endocytosis, and a dose-dependent shift in p42/44 mitogen-activated protein kinase activation and chemotaxis. Biochem. J. 352(Pt 2), 399-407. 

Seifert, R., and Wenzel-Seifert, K. (2003). The human formyl peptide receptor as model system for constitutively active G-protein-coupled receptors. Life Sci. 73, 2263-2280. 

Multiple mechanisms are probably involved in immune-modulating effects of AMPs. A variety of receptors has been described for cathelicidins, however, only one biological function, that of LL-37-mediated chemotaxis of human peripheral blood leukocytes, is associated with a known receptor (formyl peptide receptor like 1), [187]. Human BD-2 recruits mast cells and LL-37 activates epithelial cells through at least 2 classes of receptors [183,202], LL-37 transactivates epidermal growth factor receptor (EGFR) and promotes the release of IL-ip [203], and LL-37-induced maturation of LPS-primed monocytes requires the P2X(7)... 

Schultz. P. et al. (1992) Complementation of formyl peptide receptor-mediated signal transduction in )ferK us laevls oocytes. Biocham.J.. 2S4 (Pt 1). 207-212. Torrini. I. era/. (1996) ModiHed chemotactic peptides synthesis, conformation, and activity of HCO-Thp-Ac6c-Phe-OMe. Biopotymen. 39. yil-Zyi. 

The platelet activating factor receptor as a GPCR (rhodopsin family) is possibly also a promiscuous receptor for CKs. The same can be considered for the chemoattractant receptors, complement 5 anaphylatoxin receptor, and FPR/FMLPR (N-formyl peptide receptor). 

Fiore S, Serhan CN (1995) Lipoxin A4 receptor activation is distinct from that of the formyl peptide receptor in myeloid cells inhibition of CDll/18 expression by lipoxin A4-lipoxin A4 receptor interaction. Biochemistry 34 16678-16686... 

This table is intended to hold results of assays testing compounds in reg-istry.structure for activity as human immunodeficiency virus (HIV) protease inhibitors. As new assays are added, the test results can be added to newly created tables with similar definitions. For example, there might be tables for HIV reverse transcriptase inhibitors stored in a table named hiv.rt. Other assay results might be stored in new schemas, for example, fpr.htfc for high-throughput flow cytometry results for the formyl peptide receptor (FPR), or f pr.ca for FPR cell adhesion assay results. Each of these tables would have columns of data named and typed appropriately for each assay. Each table would have a column containing a compound id that references compounds in the registry, structure table. 

NKIR Substance P (SP) SP induces neutrophil chemotaxis under agarose and transmigration through fibroblast monolayers [118, 160]. Substance P is a neuropeptide known to have high affinity for the neurokinin 1 receptor, a G-protein coupled receptor [400]. However it is not clear if this receptor mediates its activity in neutrophils. Although NKIR antagonists block many of the effects of SP on neutrophils (e.g., [ 160]), there is evidence that SP binds to the N-formyl peptide receptor [230], and alone it can penetrate a membrane bilayer and activate G-proteins [252]. 

Many signaling events are triggered in neutrophils by activation of the chemoattractant receptors, including G-protein activation, lipid remodeling, protein kinase activation, and calcium elevation. Extensive work has been done to delineate the signaling mechanisms activated by the N-formyl peptide receptor, although the story is still incomplete. These pathways are complicated with crosstalk and feedback, and the many components of migration may require coordination of multiple arms of... 

Studies of the P2-adrenergic receptor system demonstrate that activation of the MAPK cascade results from assembly of MAPK enzymes on phosphorylated receptor- 3-arrestin scaffolds [304, 305]. However, this does not appear to be the case for the N-formyl peptide receptor, since MAPK activation is G-protein-dependent [ 19, 59] whereas receptor phosphorylation is G-protein-independent [315]. 

Prossnitz, E.R. (1997). Desensitization of N-formyl peptide receptor-mediated activation is dependent upon receptor phosphorylation. J. Biol. Chem. 272, 15213-15219. 

The production of N-formylated proteins is a characteristic specific to bacteria and, therefore, an obvious target for the human immune system. It has been shown that professional phagocytes, the first line of defence against invading microorganisms, express receptors that recognise N-formylated peptides [12], and that activation of these receptors mediates migration of... 

The formylated peptide fMet-Leu-Phe is probably the most commonly-used activator of neutrophils in vitro. It is used as a model agonist to study receptor-mediated processes, generating intracellular signalling molecules that then activate cell functions. This compound can, depending upon the concentration used, activate many varied functions, such as chemotaxis, aggregation, reactive oxidant production, cytoskeletal changes and (particularly in combination with cytochalasin B) degranulation. 

While GRK2, 3, and 5, phosphorylation has been associated with agonist activation of many receptors (44,137), only discrete regions of phosphorylation that are attributable to one specific enzyme appear to be essential for desensitization (122). With respect to the P -adrenergic (138-141), the dopamine D, (122), the p-opioid (142), the 5-opioid (143), the aj -adrenergic (133), the Aj and adenosine (144-146), and the N-formyl peptide (134) receptors, the motifs may be located in the carboxyl tail. 

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