The Role of the Pleckstrin Homology Domain-containing Protein CKIP-1 in Activation of p21-activated Kinase 1 (PAK1)

Upon growth factor stimulation, PAK1 is recruited to the plasma membrane and activated by a mechanism that requires its phosphorylation at Ser-223 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, 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-CK2-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

The Journal of biological chemistry 2015 Jul 09 [Epub]

Yong-Bae Kim, Yong Jae Shin, Adhiraj Roy, Jeong-Ho Kim

From the Department of Biochemistry and Molecular Medicine, The George Washington University Medical Center, Washington, DC 20037 and , Samsung Biomedical Research Institute and Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea , From the Department of Biochemistry and Molecular Medicine, The George Washington University Medical Center, Washington, DC 20037 and , From the Department of Biochemistry and Molecular Medicine, The George Washington University Medical Center, Washington, DC 20037 

PubMed

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