title: Synthetic peptide MMK-1 is a highly specific chemotactic agonist for leukocyte FPRL1.
abstract: Human phagocytic leukocytes express the seven-transmembrane G-protein-coupled receptors formyl peptide receptor (FPR) and FPR-like 1 (FPRL1). MMK-1, a synthetic peptide derived from a random peptide library, is reported to induce calcium mobilization specifically in human FPRL1 gene-transfected cells. However, its actions on human phagocytic leukocytes remain poorly defined. We found that MMK-1 is a potent chemotactic and calcium-mobilizing agonist for human monocytes, neutrophils, and FPRL1-transfected human embryonic kidney (HEK) 293 cells but is inactive in cells transfected with FPR. MMK-1 also activated HEK 293 cells transfected with FPR2, a mouse counterpart of human FPRL1. Furthermore, MMK-1 increased pertussis toxin-sensitive production of inflammatory cytokines in human monocytes. MMK-1 signaling in human phagocytes was completely desensitized by a well-defined FPRL1 agonist, suggesting that FPRL1 is likely a receptor that mediates the action of MMK-1 in primary cells. Since MMK-1 is one of the most potent FPRL1-specific agonists identified so far, it can serve as a modulator of the host defense and a useful agent for further studying the signaling and function of FPRL1.
authors: Laboratory of Molecular Immunoregulation, Division of Basic Sciences, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201, USA.
authors: J Y
authors: JY
authors: Hu
authors: Y
authors: Y
authors: Le
authors: W
authors: W
authors: Gong
authors: N M
authors: NM
authors: Dunlop
authors: J L
authors: JL
authors: Gao
authors: P M
authors: PM
authors: Murphy
authors: J M
authors: JM
authors: Wang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002630:Chemotactic Factors / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D044067:Receptors, Lipoxin; D018000:Receptors, Peptide / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D014162:Transfection
chemical_list: D002630:Chemotactic Factors; D016207:Cytokines; C105101:FPR2 protein, human; C408903:MMK-1 peptide; D010455:Peptides; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D044067:Receptors, Lipoxin; D018000:Receptors, Peptide; D002118:Calcium