A role for Jun-N-terminal kinase in anoikis; suppression by bcl-2 and crmA.
A role for Jun-N-terminal kinase in anoikis; suppression by bcl-2 and crmA.
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Jun-N末端激酶在Anoikis中的作用； Bcl-2和CRMA抑制。
DOI：
10.1083/jcb.135.5.1377
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发表时间：
1996-12
影响因子：
7.8
通讯作者：
Sicks, S
中科院分区：
文献类型：
--
作者：
Frisch, SM;Vuori, K;Kelaita, D;Sicks, S
细胞外基质和特定同源整合素之间相互作用的破坏触发上皮细胞的凋亡，这一过程称为“失巢凋亡”。为了理解失巢凋亡，正在探索上皮细胞整合素信号传导和凋亡调节蛋白之间的联系。我们在此报告，上皮细胞从基质中分离后早期激活Jun-N-末端激酶（JNKs;也称为应激激活蛋白激酶），其也被其他凋亡刺激激活。失巢凋亡需要该途径的活性。对细胞悬浮的另一个早期反应是ICE相关的半胱氨酸蛋白酶ICE/LAP 3的激活;这种激活和失巢凋亡被ICE蛋白酶抑制剂crmA抑制。bcl-2的过表达也抑制ICE/LAP 3的激活。令人惊讶的是，bcl-2和crmA减弱了细胞悬浮后JNK的活化，表明JNK途径直接或间接受蛋白水解调节。此外，JNK途径的阻断减弱了ICE/LAP 3的激活，表明ICE和JNK系统之间存在正反馈循环。这些结果表明失巢凋亡中的信息流顺序为：整合素->bcl-2/bax->（ICE-蛋白酶<->JNK）->凋亡。细胞-细胞相互作用，这是以前显示敏感的细胞失巢凋亡，导致bcl-2 mRNA下调，下游凋亡信号的一个容许事件。
The disruption of interactions between extracellular matrix and specific cognate integrins triggers apoptosis in epithelial cells, in a process termed "anoikis." To understand anoikis, the connections between epithelial cell integrin signaling and the apoptosis-regulatory proteins are being explored. We report herein that early after detachment from matrix, epithelial cells activate Jun-N-Terminal Kinases (JNKs; alternatively known as Stress-activated Protein Kinases), which are also activated by other apoptotic stimuli. The activity of this pathway was required for anoikis. Another early response to cell suspension was the activation of the ICE-related cysteine protease, ICE/LAP3; this activation and anoikis were suppressed by the ICE-protease inhibitor, crmA. The overexpression of bcl-2 suppressed ICE/LAP3 activation as well. Surprisingly, bcl-2 and crmA attenuated the activation of JNKs following cell suspension, suggesting that the JNK pathway is regulated directly or indirectly by proteolysis. In addition, the blockage of the JNK pathway attenuated the activation of ICE/LAP3, suggesting a positive feedback loop between the ICE and JNK systems. These results indicate the following sequence of information flow in anoikis: integrins-->bcl-2/bax-->(ICE-proteases<- ->JNK)-->apopt osis. Cell-cell interactions, which were previously shown to sensitize cells to anoikis, caused bcl-2 mRNA to be downregulated, a permissive event for downstream apoptotic signaling.
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影响因子：
7.8
作者：
Frisch, S M
通讯作者：
Frisch, S M
DOI：
10.1083/jcb.134.1.13
发表时间：
1996-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Grimm S;Bauer MK;Baeuerle PA;Schulze-Osthoff K
通讯作者：
Schulze-Osthoff K
DOI：
10.1083/jcb.127.2.537
发表时间：
1994-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Re F;Zanetti A;Sironi M;Polentarutti N;Lanfrancone L;Dejana E;Colotta F
通讯作者：
Colotta F
影响因子：
4.8
作者：
HANADA, M;AIMESEMPE, C;REED, JC
通讯作者：
REED, JC
影响因子：
56.9
作者：
LANGECARTER, CA;PLEIMAN, CM;JOHNSON, GL
通讯作者：
JOHNSON, GL