Document Type
Journal Article
Publication Date
Summer 7-9-2015
Journal
Journal of Biological Chemistry
Volume
290
Issue
34
Inclusive Pages
21076-85
DOI
10.1074/jbc.M115.675124
Keywords
Cell Transformation, Neoplastic--genetics; Epithelial Cells--metabolism; Gene Expression Regulation, Neoplastic; Intracellular Signaling Peptides and Proteins--genetics; Prostate--metabolism; p21-Activated Kinases--genetics
Abstract
Upon growth factor stimulation, PAK1 is recruited to the plasma membrane and activated by a mechanism that requires its phosphorylation at S223 by the protein kinase CK2. However, the upstream signaling molecules that regulate this phosphorylation event are not clearly defined. Here, we demonstrate a major role of the CK2α-interacting protein CKIP-1 in activation of PAK1. CK2α, CKIP-1 and PAK1 are translocated to membrane ruffles in response to the epidermal growth factor (EGF), where CKIP-1 mediates the interaction between CK2α, and PAK1 in a PI3K-dependent manner. Consistently, we observe that PAK1 mediates phosphorylation and modulation of the activity of p41-Arc, one of its plasma membrane substrate, in a fashion that requires PI3K and CKIP-1. Moreover, CKIP-1 knockdown or PI3K inhibition suppresses PAK1-mediated cell migration and invasion, demonstrating the physiological significance of the PI3K-CKIP-1-CK2α-PAK1 signaling pathway. Taken together, these findings identify a novel mechanism for the activation of PAK1 at the plasma membrane, which is critical for cell migration and invasion.
APA Citation
Yong-Bae Kim, Yong Jae Shin, Adhiraj Roy, and Jeong-Ho Kim. (2015). The Role of the Pleckstrin Homology Domain-containing Protein CKIP-1 in Activation of p21-activated Kinase 1 (PAK1). Journal of Biological Chemistry,
Peer Reviewed
1
Open Access
1
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Biology Commons, Cancer Biology Commons, Cell Biology Commons
Comments
This research was originally published in the Journal of Biological Chemistry. Kim, Y., Shin, Y., Roy, A., Kim, J. The Role of the Pleckstrin Homology Domain-Containing Protein CKIP-1 in Activation of p21-activated Kinase 1 (PAK1).. Journal of Biological Chemistry. 2015; [epub ahead of print]. © the American Society for Biochemistry and Molecular Biology.