Monocyte chemotactic protein 4 (MCP-4), a novel structural and functional analogue of MCP-3 and eotaxin.

Monocyte chemotactic protein 4 (MCP-4), a novel structural and functional analogue of MCP-3 and eotaxin.
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DOI:
10.1084/jem.183.5.2379
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发表时间:
1996-05-01
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Baggiolini M
Baggiolini M
中科院分区:
其他
文献类型:
--
作者:
Uguccioni M;Loetscher P;Forssmann U;Dewald B;Li H;Lima SH;Li Y;Kreider B;Garotta G;Thelen M;Baggiolini M

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从人胎儿RNA构建的文库中鉴定了一种新的人CC趋化因子互补DNA,将其克隆到杆状病毒载体中,并在Sf 9昆虫细胞中表达。释放的成熟重组蛋白具有pyro- QPDALNVPSTC的NH 2-末端序列。由75个氨基酸组成。少量的77和82个残基的两种变体(NH 2末端:LAQPDA.和FNPQGLAQPDA.)也被释放了。新的趋化因子被命名为单核细胞趋化蛋白4(MCP-4),其变体被命名为(LA)MCP-4和(FNPQGLA)MCP-4。MCP-4与三种已知的单核细胞趋化蛋白共有焦谷氨酸脯氨酸NH 2-末端基序和56-61%的序列同一性,并且与嗜酸性粒细胞趋化因子有60%的同一性。它与MCP-3和eotaxin具有显著的功能相似性。与MCP-3一样,MCP-4是对单核细胞和T淋巴细胞高效的化学引诱物。在这些细胞上,它与识别MCP-1、MCP-3和RANTES的受体结合。在嗜酸性粒细胞上,MCP-4具有与MCP-3、RANTES和嗜酸性粒细胞趋化因子相似的功效和效力。它与嗜酸性粒细胞趋化因子共享受体,并显示与这种嗜酸性粒细胞选择性趋化因子的完全交叉脱敏。在这两种变体中,只有(LA)MCP-4可以以足够的量纯化用于测试,并且发现其效力比MCP-4本身低至少30倍。这表明具有MCP的特征性NH 2末端的75个残基形式是生物学相关的种类。
A novel human CC chemokine complementary DNA was identified in a library constructed from human fetal RNA, cloned into a baculovirus vector, and expressed in Sf9 insect cells. The mature recombinant protein that was released had the NH2-terminal sequence pyro- QPDALNVPSTC...and consisted of 75 amino acids. Minor amounts of two variants of 77 and 82 residues (NH2 termini: LAQPDA...and FNPQGLAQPDA...) were released as well. The novel chemokine was designated monocyte chemotactic protein 4 (MCP-4) and the variants were designated (LA)MCP-4 and (FNPQGLA)MCP-4. MCP-4 shares the pyroglutamic acidproline NH2-terminal motif and 56-61% sequence identity with the three known monocyte chemotactic proteins and is 60% identical to eotaxin. It has marked functional similarities to MCP-3 and eotaxin. Like MCP-3, MCP-4 is a chemoattractant of high efficacy for monocytes and T lymphocytes. On these cells, it binds to receptors that recognize MCP-1, MCP-3, and RANTES. On eosinophils, MCP-4 has similar efficacy and potency as MCP-3, RANTES, and cotaxin. It shares receptors with eotaxin and shows full cross-desensitization with this cosinophil- selective chemokine. Of the two variants, only (LA)MCP-4 could be purified in sufficient quantities for testing and was found to be at least 30-fold less potent than MCP-4 itself. This suggests that the 75- residue form with the characteristic NH2 terminus of an MCP is the biologically relevant species.
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