Signal transduction involved in MCP-1-mediated monocytic transendothelial migration
Signal transduction involved in MCP-1-mediated monocytic transendothelial migration
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DOI：
10.1182/blood.v97.2.359
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发表时间：
2001-01-15
期刊：
影响因子：
20.3
通讯作者：
Schmid-Alliana, A
中科院分区：
文献类型：
--
作者：
Cambien, B;Pomeranz, M;Schmid-Alliana, A
单核细胞趋化蛋白-1（MCP-1）是单核细胞和T淋巴细胞的主要趋化因子。Mono-Mac 6细胞系用于检查与MCP-1介导的单核细胞跨内皮迁移相关的MCP-1受体介导的信号转导事件。MCP-1以不同的时程刺激细胞外信号相关激酶（ERK 1和ERK 2）和应激活化蛋白激酶SAPK 1/JNK 1和SAPK 2/p38的激活被Piceatannol阻断，表明其受Syk激酶的调节，而SAPK 2/p38的激活被PP 2抑制，表明其受Src样激酶的上游调节。ERK激活对PP 2和Piceatannol不敏感。Go/Gi蛋白阻断剂百日咳毒素可阻断MCP-1诱导的ERK激活，但对SAPK 1/JNK 1和SAPK 2/p38激活无影响。这些结果强调了Go/Gi蛋白和非受体酪氨酸激酶在早期MCP-1信号传导中的重要意义。此外，MCP-1介导的趋化性和跨内皮迁移被高浓度的SB 202190（一种广泛的SAPK抑制剂）或SB 203580（一种SAPK 2/p38的特异性抑制剂）显著减弱，并被百日咳毒素处理消除。总之，这些数据表明，不同的信号通路的协调行动是必需的，以产生一个完整的响应MCP-1的单核细胞运动。(C)2001年，美国血液学会。
Monocyte chemoattractant protein-1 (MCP-1) is a major chemoattractant for monocytes and T lymphocytes. The Mono-Mac6 cell line was used to examine MCP-1 receptor-mediated signal transduction events in relation to MCP-1-mediated monocytic transendothelial migration. MCP-1 stimulates, with distinct time courses, extracellular signal-related kinases (ERK1 and ERK2) and stress-activated protein kinases (SAPK1/JNK1 and SAPK2/p38), SAPK1/JNK1 activation was blocked by piceatannol, indicating that it is regulated by Syk kinase, whereas SAPK2/p38 activation was inhibited by PP2, revealing an upstream regulation by Src-like kinases, In contrast, ERK activation was insensitive to PP2 and piceatannol. Pertussis toxin, a blocker of Go/Gi proteins, abrogated MCP-l-induced ERK activation, but was without any effect on SAPK1/JNK1 and SAPK2/p38 activation. These results underscore the major implication of Go/Gi proteins and nonreceptor tyrosine kinases in the early MCP-1 signaling, Furthermore, MCP-l-mediated chemotaxis and transendothelial migration were significantly diminished by a high concentration of SB202190, a broad SAPK inhibitor, or by SB203580, a specific inhibitor of SAPK2/p38, and abolished by pertussis toxin treatment. Altogether, these data suggest that coordinated action of distinct signal pathways is required to produce a full response to MCP-I in terms of monocytic locomotion. (C) 2001 by The American Society of Hematology.