Molecular cloning and functional expression of two monocyte chemoattractant protein 1 receptors reveals alternative splicing of the carboxyl-terminal tails.
Monocyte chemoattractant protein 1 (MCP-1) is a member of the chemokine family of cytokines that mediate leukocyte chemotaxis. The potent and specific activation of monocytes by MCP-1 may mediate the monocytic infiltration of tissues in atherosclerosis and other inflammatory diseases. We have isolated cDNAs that encode two MCP-1-specific receptors with alternatively spliced carboxyl tails. Expression of the receptors in Xenopus oocytes conferred robust mobilization of intracellular calcium in response to nanomolar concentrations of MCP-1 but not to related chemokines. The MCP-1 receptors are most closely related to the receptor for the chemokines macrophage inflammatory protein 1 alpha and RANTES (regulated on activation, normal T expressed and secreted). The identification of the MCP-1 receptor and cloning of two distinct isoforms provide powerful tools for understanding the specificity and signaling mechanisms of this important chemokine.
Charo
I F
IF
Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94141-9100.
Myers
S J
SJ
Herman
A
A
Franci
C
C
Connolly
A J
AJ
Coughlin
S R
SR
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000378:metabolism*; D003001:Cloning, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D009000:Monocytes / Q000502:physiology*; D009865:Oocytes / Q000378:metabolism; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000235:genetics*; D011994:Recombinant Proteins / Q000096:biosynthesis; D017386:Sequence Homology, Amino Acid; D014981:Xenopus
C515334:CCR2 protein, human; D018932:Chemokine CCL2; D002630:Chemotactic Factors; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D011994:Recombinant Proteins; D002118:Calcium