TY - JOUR
T1 - Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes
AU - Vadlamudi, Ratna K.
AU - Bagheri-Yarmand, Rozita
AU - Yang, Zhibo
AU - Balasenthil, Seetharaman
AU - Nguyen, Diep
AU - Sahin, Aysegul A.
AU - Den Hollander, Petra
AU - Kumar, Rakesh
N1 - Funding Information:
We thank Drs. D. Wu and A. Strasser for generously providing pSuper-EGFP-Pak1-siRNA and BimL cDNAs, respectively, and Kapil Mehta for MCF10A model cell lysates. We also thank Mahitosh Mandal for cell cycle analysis, Liana Adam for the initial microscopic experiments, and Feng Li for GST pull-down assays. This study was supported by NIH grants CA80066 and CA90970 (R.K.).
PY - 2004/6
Y1 - 2004/6
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ccr.2004.05.022
DO - 10.1016/j.ccr.2004.05.022
M3 - Article
C2 - 15193260
AN - SCOPUS:2942603255
SN - 1535-6108
VL - 5
SP - 575
EP - 585
JO - Cancer cell
JF - Cancer cell
IS - 6
ER -