MOLECULAR-CLONING AND FUNCTIONAL EXPRESSION OF 2 MONOCYTE CHEMOATTRACTANT PROTEIN-1 RECEPTORS REVEALS ALTERNATIVE SPLICING OF THE CARBOXYL-TERMINAL TAILS

MOLECULAR-CLONING AND FUNCTIONAL EXPRESSION OF 2 MONOCYTE CHEMOATTRACTANT PROTEIN-1 RECEPTORS REVEALS ALTERNATIVE SPLICING OF THE CARBOXYL-TERMINAL TAILS
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DOI:
10.1073/pnas.91.7.2752
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发表时间:
1994-03-29
影响因子:
11.1
通讯作者:
COUGHLIN, SR
COUGHLIN, SR
中科院分区:
综合性期刊1区
文献类型:
--
作者:
CHARO, IF;MYERS, SJ;COUGHLIN, SR

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单核细胞趋化蛋白1(MCP-1)是介导白细胞趋化性的细胞因子趋化因子家族的成员。MCP-1对单核细胞的有效和特异性激活可能介导动脉粥样硬化和其他炎性疾病中组织的单核细胞浸润。我们已经分离出编码两种MCP-1特异性受体的cDNA,它们具有可变剪接的羧基尾。在非洲爪蟾卵母细胞的受体表达赋予强大的动员细胞内钙响应纳摩尔浓度的MCP-1,但不相关的趋化因子。MCP-1受体与趋化因子巨噬细胞炎性蛋白1 α和RANTES(受激活调节,正常T细胞表达和分泌)的受体关系最为密切。MCP-1受体的鉴定和两种不同亚型的克隆为理解这种重要趋化因子的特异性和信号传导机制提供了有力的工具。
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 1alpha 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.