Inhibition of pp125FAK in cultured fibroblasts results in apoptosis.
Inhibition of pp125FAK in cultured fibroblasts results in apoptosis.
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DOI：
10.1083/jcb.135.5.1383
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发表时间：
1996-12
影响因子：
7.8
通讯作者：
Otey, CA
中科院分区：
文献类型：
--
作者：
Hungerford, JE;Compton, MT;Matter, ML;Hoffstrom, BG;Otey, CA
酪氨酸激酶pp125FAK被认为在整合素介导的信号转导中起重要作用。pp125 FAK在功能上和空间上与整合素相关，整合素是细胞外基质成分的细胞表面受体。虽然pp125 FAK的确切功能尚不清楚，但已经提出了两种可能性：pp125 FAK可能调节扩散或迁移细胞中粘着斑的组装，或者pp125 FAK可能参与信号转导级联以通知细胞核细胞被锚定。为了在活细胞中测试这些模型，将代表β 1尾的粘着斑激酶（FAK）结合位点的肽偶联至载体蛋白，并注射至培养的细胞中以竞争性抑制pp125FAK与内源性整联蛋白的结合，从而在逐个细胞的基础上抑制pp125FAK的活化。此外，显微注射针对邻近pp125 FAK上粘着斑靶向序列的表位的抗体，作为抑制pp125 FAK活化的替代手段。观察到当圆形细胞注射整联蛋白肽或抗FAK抗体时，细胞在注射后4小时内迅速开始糖化。这些结果表明pp125 FAK可能在抑制成纤维细胞凋亡中起关键作用。
The tyrosine kinase called pp125FAK is believed to play an important role in integrin-mediated signal transduction. pp125FAK is associated both functionally and spatially with integrins, which are the cell surface receptors for extracellular matrix components. Although the precise function of pp125FAK is not known, two possibilities have been proposed: pp125FAK may regulate the assembly of focal adhesions in spreading or migrating cells, or pp125FAK may participate in a signal transduction cascade to inform the nucleus that the cell is anchored. To test these models in living cells, a peptide representing the focal adhesion kinase (FAK)-binding site of the beta 1 tail was coupled to carrier protein and injected into cultured cells to competitively inhibit the binding of pp125FAK to endogenous integrin, thus inhibiting activation of pp125FAK on a cell-by-cell basis. In addition, an antibody directed against an epitope adjacent to the focal adhesion targeting sequence on pp125FAK was microinjected, as an alternative means of inhibiting pp125FAK activation. It was observed that when rounded cells were injected with either the integrin peptide or the anti-FAK antibody, the cells rapidly began to apoptose, within 4 h after injection. These results indicate that pp125FAK may play a critical role in suppressing apoptosis in fibroblasts.
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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：
64.5
作者：
BROOKS, PC;MONTGOMERY, AMP;CHERESH, DA
通讯作者：
CHERESH, DA
影响因子：
64.8
作者：
GUAN, JL;SHALLOWAY, D
通讯作者：
SHALLOWAY, D
DOI：
10.1073/pnas.88.19.8392
发表时间：
1991-10-01
影响因子：
11.1
作者：
KORNBERG, LJ;EARP, HS;JULIANO, RL
通讯作者：
JULIANO, RL
DOI：
10.1083/jcb.131.3.791
发表时间：
1995-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Miyamoto S;Teramoto H;Coso OA;Gutkind JS;Burbelo PD;Akiyama SK;Yamada KM
通讯作者：
Yamada KM