Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes
Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes
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DOI：
10.1016/j.ccr.2004.05.022
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发表时间：
2004-06-01
期刊：
影响因子：
50.3
通讯作者：
Kumar, R
中科院分区：
文献类型：
--
作者：
Vadlamudi, RK;Bagheri-Yarmand, R;Kumar, R
我们确定动力蛋白轻链1（DLC 1）作为p21激活激酶1（Pak 1）的生理底物。Pak 1-DLC 1相互作用在细胞存活中起重要作用，这取决于Pak 1对DLC 1在Ser 88上的磷酸化。Pak 1与DLC 1和BimL的复合物（一种促凋亡的仅含BH 3的蛋白）相关联，并使两种蛋白磷酸化。Pak 1对BimL的磷酸化可防止其与抗凋亡蛋白Bcl-2相互作用和失活。DLC 1而非DLC 1-Ser 88 Ala突变体的过表达促进乳腺癌细胞的癌性。DLC 1蛋白水平在超过90%的人类乳腺肿瘤中升高。通过Pak 1-DLC 1相互作用调节细胞存活功能代表了信号激酶可能调节癌表型的新机制。
We identified dynein light chain 1 (DLC1) as a physiologic substrate of p21-activated kinase 1 (Pak1). Pak1-DLC1 interaction plays an essential role in cell survival, which depends on Pak1's phosphorylation of DLC1 on Ser88. Pak1 associates with the complex of DLC1 and BimL, a proapoptotic BH3-only protein, and phosphorylates both proteins. Phosphorylation of BimL by Pak1 prevents it from interacting with and inactivation of Bcl-2, an antiapoptotic protein. Overexpression of DLC1 but not DLC1-Ser88Ala mutant promotes cancerous properties of breast cancer cells. DLC1 protein level is elevated in more than 90% of human breast tumors. The regulation of cell survival functions by Pak1-DLC1 interaction represents a novel mechanism by which a signaling kinase might regulate the cancerous phenotypes.