N-Formyl peptide receptor

Reported applications of SASD involve modification of lipopolysaccharide (LPS) molecules and studying their interaction with albumin and an antibody directed against LPS (Wollenweber and Morrison, 1985), identification of the murine interleukin-3 receptor and an N-formyl peptide receptor (Sorenson et al., 1986), crosslinking of factor V and Va to iodinated peptides... 

Schmitt, M., Painter, R.G., Jesaitis, A.J., Preissner, K., Sklar, L.A., and Cochrane, C.G. (1983) Photoaffinity labeling of the N-formyl peptide receptor binding site of intact human polymorphonuclear leukocytes./. Biol. Chem. 258, 649-654. 

Maestes, D. C., Potter, R. M., and Prossnitz, E. R. (1999) Differential phosphorylation paradigms dictate desensitization and internalization of the N-formyl peptide receptor. J. Biol. Chem. 274, 29791-29795. 

Boulay, F., Tardif, M., Brouchon, L., and Vignais, P. (1990) Synthesis and use of a novel N-formyl peptide derivative to isolate a human N-formyl peptide receptor cDNA. Biochem. Biophys. Res. Commun. 168,1103-1109. 

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. 

Murphy, P. M., Tiffany, H. L., McDermott, D., and Ahuja, S. K. (1993). Sequence and organization of the human N-formyl peptide receptor-encoding gene. Gene 133, 285-290. 

Prossnitz, E. R., Schreiber, R. E., Bokoch, G. M., and Ye, R. D. (1995). Binding of low affinity N-formyl peptide receptors to G protein. Characterization of a novel inactive receptor intermediate. / Biol. Chem. 270, 10686-10694. 

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). 

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... 

Desensitization and lateral segregation of receptor and G-protein Subcellular fractionation studies have revealed two plasma membrane fractions in neutrophils, based on their densities a light plasma membrane fraction and a heavy plasma membrane fraction [156]. In unstimulated cells, the light plasma membrane fraction shows concentration of the N-formyl peptide receptor and Gj-proteins. In cells desensitized by... 

Like other G-protein-coupled receptors, the N-formyl peptide receptor can be phosphorylated [8, 382], and neutrophils have a G-protein-coupled receptor kinase GRK2 (also known as P-adrenergic receptor kinase) [61, 312], Phosphorylation of the N-formyl peptide receptor in HL-60... 

In a reconstituted receptor system, phosphorylated wild-type N-formyl peptide receptors, but not nonphosphorylated receptors. 

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]. 

Just as the coupling of receptors and G-proteins in plasma membrane microdomains is regulated (see Section 9.1.2), evidence indicates that co-localization or segregation of G-proteins and effectors in membrane microdomains is a mechanism by which cell responsiveness to chemoattractant is regulated. Resting, unactivated neutrophils respond little to N-formyl peptides, however, when primed by a variety of chemical and physical conditions, these cells become very responsive [69, 166]. Studies show [166] that in unprimed cells N-formyl peptide receptors, phospholipase Cp2, and Lyn kinase predominate in the heavy plasma membrane fractions, whereas Q2 and Gj3 are in the light plasma membrane fractions. As a consequence of priming, Gj2 (but not Gjs) moves to... 

Bennett, T.A., Foutz, T.D., Gurevich, V.V., Sklar, L.A. and Prossnitz, E.R. (2001). Partial phosphorylation of the N-formyl peptide receptor inhibits G-protein association independent of arrestin binding. J. Biol. Chem. 276, 49 195-49 203. 

Hoffman, J.F., Linderman, J.J., Omann, G.M. (1996). Receptor upregulation, internalization, and interconverting receptor states critical components of a quantitative description of N-formyl peptide-receptor dynamics in the neutrophil. /. Biol. Chem. 271, 18394-18404. 

Loitto, V.-M., Rasmusson, B. and Magnusson, K.-E. (2001). Assessment of neutrophil N-formyl peptide receptors by using antibodies and fluorescent peptides. J. Leak. Biol 69, 762-771. 

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