Induction of protein tyrosine kinase 6 in mouse intestinal crypt epithelial cells promotes DNA damage-induced apoptosis.
Induction of protein tyrosine kinase 6 in mouse intestinal crypt epithelial cells promotes DNA damage-induced apoptosis.
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DOI：
10.1053/j.gastro.2009.05.054
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发表时间：
2009-09
期刊：
影响因子：
29.4
通讯作者：
Tyner AL
中科院分区：
文献类型：
--
作者：
Haegebarth A;Perekatt AO;Bie W;Gierut JJ;Tyner AL
蛋白酪氨酸激酶6（PTK 6）在胃肠道的上皮衬里中表达。PTK 6使未转化的Rat 1a成纤维细胞系对凋亡刺激物敏感。本研究的目的是确定PTK 6是否在小肠DNA损伤后调节体内细胞凋亡。对野生型和Ptk 6 −/−小鼠进行γ射线照射;在照射后0、6和72小时收集肠组织，分离蛋白质，并固定样品进行免疫组织化学分析。在照射前后检测小肠中PTK 6的表达。在野生型和Ptk 6 −/−小鼠之间比较了细胞凋亡和增殖。评估促存活信号传导蛋白的表达和活化。辐照诱导野生型小鼠小肠隐窝上皮细胞中的PTK 6。PTK 6的诱导与野生型小肠中DNA损伤诱导的细胞凋亡相对应。照射后，Ptk 6 −/−小鼠肠隐窝中的凋亡反应受损。在照射后的Ptk 6 −/−小鼠中检测到AKT和细胞外信号调节激酶（ERK）1/2的活化增加以及促凋亡蛋白BAD的抑制性磷酸化增加。在辐射后6小时，野生型小鼠的小肠对诱导凋亡的反应是代偿性增殖增加，但Ptk 6 −/−小鼠的小肠没有。PTK 6是一种应激诱导的激酶，其通过抑制促存活信号传导来促进细胞凋亡。DNA损伤后，诱导PTK 6是有效凋亡和抑制AKT和ERK 1/2所必需的。
Protein tyrosine kinase 6 (PTK6) is expressed in epithelial linings of the gastrointestinal tract. PTK6 sensitizes the non-transformed Rat1a fibroblast cell line to apoptotic stimuli. The aim of this study was to determine if PTK6 regulates apoptosis in vivo after DNA damage in the small intestine. Wild-type and Ptk6 −/− mice were subjected to γ-irradiation; intestinal tissues were collected, protein was isolated, and samples were fixed for immunohistochemical analyses at 0, 6, and 72 hours after the mice were irradiated. Expression of PTK6 was examined in the small intestine before and after irradiation. Apoptosis and proliferation were compared between wild-type and Ptk6 −/− mice. Expression and activation of pro-survival signaling proteins were assessed. Irradiation induced PTK6 in crypt epithelial cells of the small intestine in wild-type mice. Induction of PTK6 corresponded with DNA-damage induced apoptosis in the wild-type small intestine. Following irradiation, the apoptotic response was impaired in the intestinal crypts of Ptk6 −/− mice. Increased activation of AKT and extracellular signal-regulated kinase (ERK)1/2 and increased inhibitory phosphorylation of the proapoptotic protein BAD were detected in Ptk6 −/− mice after irradiation. In response to the induction of apoptosis, compensatory proliferation increased in the small intestines of wild-type mice, but not in Ptk6 −/− mice at 6 hours after irradiation. PTK6 is a stress-induced kinase that promotes apoptosis by inhibiting pro-survival signaling. After DNA damage, induction of PTK6 is required for efficient apoptosis and inhibition of AKT and ERK1/2.
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影响因子：
8
作者：
Barker, KT;Jackson, LE;Crompton, MR
通讯作者：
Crompton, MR
影响因子：
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作者：
Haegebarth, A;Nunez, R;Tyner, AL
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Tyner, AL
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作者：
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作者：
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