Document Type

Journal Article

Publication Date

Summer 7-9-2015


Journal of Biological Chemistry





Inclusive Pages





Cell Transformation, Neoplastic--genetics; Epithelial Cells--metabolism; Gene Expression Regulation, Neoplastic; Intracellular Signaling Peptides and Proteins--genetics; Prostate--metabolism; p21-Activated Kinases--genetics


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.


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.

Peer Reviewed


Open Access




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