Lack of correlation between activation of Jun-NH2-terminal kinase and induction of apoptosis after detachment of epithelial cells.
Lack of correlation between activation of Jun-NH2-terminal kinase and induction of apoptosis after detachment of epithelial cells.
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Jun-NH2-末端激酶激活与上皮细胞分离后凋亡的诱导之间缺乏相关性。
DOI：
10.1083/jcb.139.4.1017
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发表时间：
1997-11-17
影响因子：
7.8
通讯作者：
Downward, J
中科院分区：
文献类型：
--
作者：
Khwaja, A;Downward, J
上皮细胞与细胞外基质的分离导致诱导程序性细胞死亡，这一过程被称为“失巢凋亡”。最近已经报道，MDCK细胞从基质脱离导致Jun-NH 2-末端激酶（JNK）的活化，并且推测这些应激活化的蛋白激酶在失巢凋亡的诱导中起因果作用（Frisch，S.M.，K. Vuori，D. Kelaita和S.变态1996. 135：1377-1382）。我们在这里报告，虽然JNK被激活的正常MDCK细胞的脱离，表达激活的信号蛋白通常由Ras控制的细胞系的研究表明，JNK的刺激未能与诱导失巢凋亡。激活的磷酸肌醇3-OH激酶和激活的PKB/Akt保护MDCK细胞免受脱落诱导的细胞凋亡，而不抑制JNK激活。相反，激活的Raf和显性负性SEK 1（一种JNK激酶）减弱了细胞凋亡诱导的JNK激活，而不保护细胞凋亡。半胱天冬酶的肽抑制剂zVAD-fatase防止MDCK细胞失巢凋亡而不影响JNK活化。p38，一种相关的应激激活激酶，也被从基质中分离所刺激，但是用SB 203580抑制该激酶并不能防止失巢凋亡。因此，JNK或p38不太可能在上皮细胞的凋亡诱导的程序性细胞死亡中发挥直接作用。
Detachment of epithelial cells from the extracellular matrix leads to induction of programmed cell death, a process that has been termed “anoikis.” It has been reported recently that detachment of MDCK cells from matrix results in activation of Jun–NH2-terminal kinases (JNKs) and speculated that these stress activated protein kinases play a causal role in the induction of anoikis (Frisch, S.M., K. Vuori, D. Kelaita, and S. Sicks. 1996. J. Cell Biol. 135:1377–1382). We report here that although JNK is activated by detachment of normal MDCK cells, study of cell lines expressing activated signaling proteins usually controlled by Ras shows that stimulation of JNK fails to correlate with induction of anoikis. Activated phosphoinositide 3-OH kinase and activated PKB/Akt protect MDCK cells from detachment-induced apoptosis without suppressing JNK activation. Conversely, activated Raf and dominant negative SEK1, a JNK kinase, attenuate detachment-induced JNK activation without protecting from apoptosis. zVAD-fmk, a peptide inhibitor of caspases, prevents MDCK cell anoikis without affecting JNK activation. p38, a related stress-activated kinase, is also stimulated by detachment from matrix, but inhibition of this kinase with SB 203580 does not protect from anoikis. It is therefore unlikely that either JNK or p38 play a direct role in detachment-induced programmed cell death in epithelial cells.
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影响因子：
4.8
作者：
Johnson, NL;Gardner, AM;Johnson, GL
通讯作者：
Johnson, GL
影响因子：
56.9
作者：
Joneson, T;White, MA;BarSagi, D
通讯作者：
BarSagi, D
Jun-N末端激酶在Anoikis中的作用； Bcl-2和CRMA抑制。
影响因子：
7.8
作者：
Frisch, SM;Vuori, K;Kelaita, D;Sicks, S
通讯作者：
Sicks, S
影响因子：
16.2
作者：
HAM, J;BABIJ, C;RUBIN, LL
通讯作者：
RUBIN, LL
影响因子：
7.5
作者：
Marshall, CJ
通讯作者：
Marshall, CJ