Low affinity receptor for N-formyl-methionyl peptides, which are powerful neutrophils chemotactic factors. Binding of FMLP to the receptor causes activation of neutrophils. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. The activation of LXA4R could result in an anti-inflammatory outcome counteracting the actions of proinflammatory signals such as LTB4 (leukotriene B4).
Combining with an extracellular signal and transmitting the signal across the membrane by activating an associated G-protein; promotes the exchange of GDP for GTP on the alpha subunit of a heterotrimeric G-protein complex.
J. Biol. Chem. 272, 6972-6978 (1997)[PubMed:9054386]
Lipoxins (LX) are bioactive eicosanoids that activate human monocytes and inhibit neutrophils. LXA4 is rapidly converted by monocytes to inactive products, and to resist metabolism, synthetic analogs of LXA4 were designed. Here, we examined the bioactivity of several LXA4 analogs in monocytes and found, for chemotaxis, 15(R/S)-methyl-LXA4 and 15-epi-LXA4 were equal in activity, and 16-phenoxy-LXA4 was more potent than native LXA4. Both 15(R/S)-methyl-LXA4 and 16-phenoxy-LXA4 were approximately 1 log molar more potent than LXA4 in stimulating THP-1 cell adherence (EC50 approximately 1 x 10(-10) M). Dimethylamide derivatives of the LXA4 analogs also possessed agonist rather than antagonist properties for monocytes. Neither LXA4 nor 16-phenoxy-LXA4 affected monocyte-mediated cytotoxicity. We cloned an LXA4 receptor from THP-1 cells identical to that found in PMN. Evidence of receptor-mediated function of LXA4 and the stable analogs in monocytes included desensitization of intracellular calcium mobilization to a second challenge by equimolar concentrations of these analogs, but not to LTB4. Increases in [Ca2+]i by LXA4 and the analogs were specifically inhibited by an antipeptide antibody to the LXA4 receptor; and both LXA4- and analog-induced adherence and increments in Ca2+ were sensitive to pertussis toxin. Together, these results indicate that the LXA4 stable analogs are potent monocyte chemoattractants and are more potent than native LXA4 in stimulating THP-1 cell adherence, at subnanomolar concentrations. Moreover, they provide additional evidence that the LXA4 stable analogs retain selective bioactivity in monocytes and are valuable instruments for examining the functions and modes of action of LXA4.
J. Biol. Chem. 272, 6972-6978 (1997)[PubMed:9054386]
Lipoxins (LX) are bioactive eicosanoids that activate human monocytes and inhibit neutrophils. LXA4 is rapidly converted by monocytes to inactive products, and to resist metabolism, synthetic analogs of LXA4 were designed. Here, we examined the bioactivity of several LXA4 analogs in monocytes and found, for chemotaxis, 15(R/S)-methyl-LXA4 and 15-epi-LXA4 were equal in activity, and 16-phenoxy-LXA4 was more potent than native LXA4. Both 15(R/S)-methyl-LXA4 and 16-phenoxy-LXA4 were approximately 1 log molar more potent than LXA4 in stimulating THP-1 cell adherence (EC50 approximately 1 x 10(-10) M). Dimethylamide derivatives of the LXA4 analogs also possessed agonist rather than antagonist properties for monocytes. Neither LXA4 nor 16-phenoxy-LXA4 affected monocyte-mediated cytotoxicity. We cloned an LXA4 receptor from THP-1 cells identical to that found in PMN. Evidence of receptor-mediated function of LXA4 and the stable analogs in monocytes included desensitization of intracellular calcium mobilization to a second challenge by equimolar concentrations of these analogs, but not to LTB4. Increases in [Ca2+]i by LXA4 and the analogs were specifically inhibited by an antipeptide antibody to the LXA4 receptor; and both LXA4- and analog-induced adherence and increments in Ca2+ were sensitive to pertussis toxin. Together, these results indicate that the LXA4 stable analogs are potent monocyte chemoattractants and are more potent than native LXA4 in stimulating THP-1 cell adherence, at subnanomolar concentrations. Moreover, they provide additional evidence that the LXA4 stable analogs retain selective bioactivity in monocytes and are valuable instruments for examining the functions and modes of action of LXA4.
A cDNA of 1650 base pairs was isolated by screening an HL-60 granulocyte library with an N-formyl peptide receptor (NFPR) cDNA probe under low stringency conditions. The cDNA encodes a protein of 351 amino acids tentatively named FPR2, with a calculated molecular weight of 39 kDa. Sequence analysis revealed that FPR2 is 69% identical in sequence to the human NFPR and shares extensive homology to several other chemoattractant receptors. FPR2 expressed in transfected cells mediated formyl peptide-stimulated calcium mobilization at micromolar concentrations of ligand. FPR2 messenger is detected in granulocytic HL-60 cells, but not in undifferentiated HL-60 cells. These findings suggest that FPR2 is a novel receptor for formyl peptide ligand and a new member of the chemoattractant receptor gene family.
The directed movement of a motile cell or organism, or the directed growth of a cell guided by a specific chemical concentration gradient. Movement may be towards a higher concentration (positive chemotaxis) or towards a lower concentration (negative chemotaxis).
A series of molecular signals that proceeds with an activated receptor promoting the exchange of GDP for GTP on the alpha-subunit of an associated heterotrimeric G-protein complex. The GTP-bound activated alpha-G-protein then dissociates from the beta- and gamma-subunits to further transmit the signal within the cell. The pathway begins with receptor-ligand interaction, or for basal GPCR signaling the pathway begins with the receptor activating its G protein in the absence of an agonist, and ends with regulation of a downstream cellular process, e.g. transcription.
J. Biol. Chem. 272, 6972-6978 (1997)[PubMed:9054386]
Lipoxins (LX) are bioactive eicosanoids that activate human monocytes and inhibit neutrophils. LXA4 is rapidly converted by monocytes to inactive products, and to resist metabolism, synthetic analogs of LXA4 were designed. Here, we examined the bioactivity of several LXA4 analogs in monocytes and found, for chemotaxis, 15(R/S)-methyl-LXA4 and 15-epi-LXA4 were equal in activity, and 16-phenoxy-LXA4 was more potent than native LXA4. Both 15(R/S)-methyl-LXA4 and 16-phenoxy-LXA4 were approximately 1 log molar more potent than LXA4 in stimulating THP-1 cell adherence (EC50 approximately 1 x 10(-10) M). Dimethylamide derivatives of the LXA4 analogs also possessed agonist rather than antagonist properties for monocytes. Neither LXA4 nor 16-phenoxy-LXA4 affected monocyte-mediated cytotoxicity. We cloned an LXA4 receptor from THP-1 cells identical to that found in PMN. Evidence of receptor-mediated function of LXA4 and the stable analogs in monocytes included desensitization of intracellular calcium mobilization to a second challenge by equimolar concentrations of these analogs, but not to LTB4. Increases in [Ca2+]i by LXA4 and the analogs were specifically inhibited by an antipeptide antibody to the LXA4 receptor; and both LXA4- and analog-induced adherence and increments in Ca2+ were sensitive to pertussis toxin. Together, these results indicate that the LXA4 stable analogs are potent monocyte chemoattractants and are more potent than native LXA4 in stimulating THP-1 cell adherence, at subnanomolar concentrations. Moreover, they provide additional evidence that the LXA4 stable analogs retain selective bioactivity in monocytes and are valuable instruments for examining the functions and modes of action of LXA4.
The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages.
J. Biol. Chem. 272, 6972-6978 (1997)[PubMed:9054386]
Lipoxins (LX) are bioactive eicosanoids that activate human monocytes and inhibit neutrophils. LXA4 is rapidly converted by monocytes to inactive products, and to resist metabolism, synthetic analogs of LXA4 were designed. Here, we examined the bioactivity of several LXA4 analogs in monocytes and found, for chemotaxis, 15(R/S)-methyl-LXA4 and 15-epi-LXA4 were equal in activity, and 16-phenoxy-LXA4 was more potent than native LXA4. Both 15(R/S)-methyl-LXA4 and 16-phenoxy-LXA4 were approximately 1 log molar more potent than LXA4 in stimulating THP-1 cell adherence (EC50 approximately 1 x 10(-10) M). Dimethylamide derivatives of the LXA4 analogs also possessed agonist rather than antagonist properties for monocytes. Neither LXA4 nor 16-phenoxy-LXA4 affected monocyte-mediated cytotoxicity. We cloned an LXA4 receptor from THP-1 cells identical to that found in PMN. Evidence of receptor-mediated function of LXA4 and the stable analogs in monocytes included desensitization of intracellular calcium mobilization to a second challenge by equimolar concentrations of these analogs, but not to LTB4. Increases in [Ca2+]i by LXA4 and the analogs were specifically inhibited by an antipeptide antibody to the LXA4 receptor; and both LXA4- and analog-induced adherence and increments in Ca2+ were sensitive to pertussis toxin. Together, these results indicate that the LXA4 stable analogs are potent monocyte chemoattractants and are more potent than native LXA4 in stimulating THP-1 cell adherence, at subnanomolar concentrations. Moreover, they provide additional evidence that the LXA4 stable analogs retain selective bioactivity in monocytes and are valuable instruments for examining the functions and modes of action of LXA4.
Protein involved in the movement of a cell, or organism, along a concentration gradient of a chemotactic agent, such as a protein which causes, mediates or responds to chemotaxis. Chemotactic molecules such as sugars, peptides, cell metabolites, cell-wall or membrane lipids bind to cell surface receptors and trigger activation of intracellular signaling pathways, as well as remodeling of the cytoskeleton through the activation or inhibition of various actin-binding proteins.
Receptors which transduce extracellular signals across the cell membrane. At the external side they receive a ligand (a photon in case of opsins), and at the cytosolic side they activate a guanine nucleotide-binding (G) protein. These receptors are hydrophobic proteins that cross the membrane seven times.
A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.
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