Outside-in signal transmission by conformational changes in integrin Mac-1.
Outside-in signal transmission by conformational changes in integrin Mac-1.
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DOI：
10.4049/jimmunol.0900983
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发表时间：
2009-11-15
期刊：
影响因子：
--
通讯作者：
Kim M
中科院分区：
文献类型：
--
作者：
Lefort CT;Hyun YM;Schultz JB;Law FY;Waugh RE;Knauf PA;Kim M
与整合素连接相关或由整合素连接触发的细胞内信号可以控制细胞的存活、分化、增殖和迁移。尽管越来越多的证据表明构象变化调节整合素与其配体的亲和力，但整合素结构如何调节信号从细胞外到细胞内部的传递仍然是个谜。利用荧光共振能量转移，我们研究了整合素Mac-1的构象变化是否足以在人中性粒细胞中传递由外向内的信号。配体占位或激活抗体结合诱导的Mac-1构象激活，而不是整合素聚集，触发了细胞内蛋白酪氨酸磷酸化的相似模式，包括Akt磷酸化，并抑制了自发性中性粒细胞凋亡，表明整体构象变化在依赖Mac-1的自外向内信号转导中起关键作用。在中性粒细胞和髓系K562细胞中，配体ICAM-1或激活的抗体结合促进了Mac-1胞外区的弹簧状延伸和αM和β2亚单位胞浆尾部的分离，这是整合素激活的两个结构特征。这些数据表明，在Mac-1由外而内信号的产生过程中，全球构象变化是首要的。
Intracellular signals associated with or triggered by integrin ligation can control cell survival, differentiation, proliferation, and migration. Despite accumulating evidence that conformational changes regulate integrin affinity to its ligands, how integrin structure regulates signal transmission from the outside to the inside of the cell remains elusive. Using fluorescence resonance energy transfer, we addressed whether conformational changes in integrin Mac-1 are sufficient to transmit outside-in signals in human neutrophils. Mac-1 conformational activation induced by ligand occupancy or activating Ab binding, but not integrin clustering, triggered similar patterns of intracellular protein tyrosine phosphorylation, including Akt phosphorylation, and inhibited spontaneous neutrophil apoptosis, indicating that global conformational changes are critical for Mac-1-dependent outside-in signal transduction. In neutrophils and myeloid K562 cells, ligand ICAM-1 or activating Ab binding promoted switchblade-like extension of the Mac-1 extracellular domain and separation of the αM and β2 subunit cytoplasmic tails, two structural hallmarks of integrin activation. These data suggest the primacy of global conformational changes in the generation of Mac-1 outside-in signals.
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影响因子：
3.4
作者：
Chigaev, A;Buranda, T;Sklar, LA
通讯作者：
Sklar, LA
影响因子：
32.4
作者：
Nishida, Noritaka;Xie, Can;Springer, Timothy A.
通讯作者：
Springer, Timothy A.
影响因子：
64.5
作者：
Emsley, J;Knight, CG;Liddington, RC
通讯作者：
Liddington, RC
影响因子：
56.9
作者：
MIYAMOTO, S;AKIYAMA, SK;YAMADA, KM
通讯作者：
YAMADA, KM
DOI：
10.4049/jimmunol.0803388
发表时间：
2009-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hyun YM;Chung HL;McGrath JL;Waugh RE;Kim M
通讯作者：
Kim M