Cloning and functional expression of mCCR2, a murine receptor for the C-C chemokines JE and FIC.
The C-C chemokines human monocyte chemoattractant protein-1 and -3 (MCP-1 and MCP-3) and mouse JE and FIC are potent activators of monocytes. Several receptors for MCP-1 and MCP-3 have been cloned from human monocytic cell lines, and one of these receptors, CCR2B, binds both MCP-l and MCP-3. Thus far, no murine receptors for JE or FIC have been reported. We have cloned a novel murine C-C chemokine receptor, designated mouse CCR2 (mCCR2), from the mouse monocyte cell line WEHI265.1. The predicted 373-amino acid sequence of mCCR2 shows highest identity (80%) with CCR2B. When stably expressed in human embryonic kidney 293 cells, mCCR2 specifically bound 125I-JE with high affinity. FIC was less potent than JE in competing 125I-JE binding to mCCR2-expressing cells, while three other mouse chemokines, MIP-1alpha, C10, and N51/KC, did not compete. mccr2 mRNA expression was detected in elicited peritoneal macrophages as well as in several mouse organs. The cloning of mCCR2 provides an important tool to investigate monocyte/macrophage responses to JE and FIC, to identify other targets for their action, and potentially to study models of CCR2 function in the mouse.
Kurihara
T
T
Department of Oncology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000, USA.
Bravo
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R
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018932:Chemokine CCL2 / Q000378:metabolism*; D054410:Chemokine CCL7; D003001:Cloning, Molecular; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000235:genetics* / Q000378:metabolism
C515450:CCL7 protein, human; C515334:CCR2 protein, human; C515451:Ccl7 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D054410:Chemokine CCL7; D016207:Cytokines; D017874:Immediate-Early Proteins; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine