动力蛋白轻链1，一种与p21激活激酶1相互作用的底物，可促进癌性表型。

Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes.

作者信息

Vadlamudi Ratna K, Bagheri-Yarmand Rozita, Yang Zhibo, Balasenthil Seetharaman, Nguyen Diep, Sahin Aysegul A, den Hollander Petra, Kumar Rakesh

机构信息

Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

出版信息

Cancer Cell. 2004 Jun;5(6):575-85. doi: 10.1016/j.ccr.2004.05.022.

DOI:10.1016/j.ccr.2004.05.022

PMID:15193260

Abstract

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.

摘要

我们确定动力蛋白轻链1（DLC1）是p21激活激酶1（Pak1）的生理底物。Pak1与DLC1的相互作用在细胞存活中起重要作用，这取决于Pak1对DLC1第88位丝氨酸的磷酸化。Pak1与DLC1和BimL（一种仅含BH3结构域的促凋亡蛋白）的复合物结合，并使这两种蛋白磷酸化。Pak1对BimL的磷酸化可防止其与抗凋亡蛋白Bcl-2相互作用并使其失活。DLC1的过表达而非DLC1-Ser88Ala突变体促进乳腺癌细胞的癌性特性。在超过90%的人类乳腺肿瘤中，DLC1蛋白水平升高。Pak1与DLC1的相互作用对细胞存活功能的调节代表了一种信号激酶可能调节癌性表型的新机制。