N-formylated peptides

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... 

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. 

N-formyl-peptides (FP) are G-protein coupled receptors and members of the phagocyte chemotactic receptor family, which are involved in inflammatory processes. N-formyl-peptides are indicators of the presence of bacteria or damage to host cells in mitochondria. Receptor binding is giving a signal for infection... 

The desensitization of most GPCRs appears to be dependent on the carboxyl tail or third intracellular loop regions. For example, the cx -adrenergic (132), the a,g-adrenergic (133), the N-formyl peptide (134), and the M2 muscarinic acetylcholine (135,136) receptors aU contain clusters of residues in the third intracellular loop that are required for desensitization. 

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. 

The normal internalization of the wild-type receptor, defined as a loss of cell surface receptors (measured by decreased maximal binding or B ), was unaffected for the desensitization-deficient Thr mutant (see Fig. 6.4C,D) but may have been affected when distal carboxyl terminal residues were mutated (see Fig. 6.3). Therefore some, although not all, GPCRs show radical dissociation between desensitization and internalization. This is found not only in the dopamine Dj receptor (122) but also in the N-formyl peptide (134), the CBl cannabinoid (17), and the M2 muscarinic (155) receptors. 

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. 

Since all peripheral blood neutrophils have chemoattractant receptors for N-formyl peptide, the entire population of neutrophils should exhibit a concentration-dependent shift in fluorescence intensity when exposed to FP-Fl. The mean channel values of the normal distribution fluorescence histograms are recorded and plotted vs the concentration of fluorescent FMLPK-Fl (Fig. 2). The data presented in Fig. 2 are from an... 

Kikuchi A, Kuroda S, Sasaki T et al. (1992) Functional interactions of stimulatory and inhibitory GDP/GTP exchange proteins and their common substrate small GTP-binding protein. In J. Biol. Chem. 26iJ-. 14611-5 Kimura K, Ito M, Amano M etal. (1996) Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase). In Science 273 245-8 Koch G, Norgauer J, Aktories K (1994) ADP-ribosylation of Rho by Clostridium limosum exoenzyme affects basal but not N-formyl-peptide-stimulated actin... 

Allen, R.A. era/. (1989) Identification of a human neutrophil protein of Mr 24 000 that binds N-formyl peptides co-sedimentation with specitic granules. Biochim. Biophys. Acta.,991.123-133. 

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). 

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