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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Roy, Adhiraj Kim, Jeong-ho Kim, Yong-bae Shin, Yong Jae |
| Description | Author Affiliation: Kim YB ( From the Department of Biochemistry and Molecular Medicine, The George Washington University Medical Center, Washington, DC 20037 and.); Shin YJ ( Samsung Biomedical Research Institute and Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea.); Roy A ( From the Department of Biochemistry and Molecular Medicine, The George Washington University Medical Center, Washington, DC 20037 and.); Kim JH ( From the Department of Biochemistry and Molecular Medicine, The George Washington University Medical Center, Washington, DC 20037 and jh_kim@gwu.edu.) |
| Abstract | 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 CK2 -interacting protein CKIP-1 in activation of PAK1. CK2 , CKIP-1, and PAK1 are translocated to membrane ruffles in response to the epidermal growth factor (EGF), where CKIP-1 mediates the interaction between CK2 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. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 34 |
| Volume Number | 290 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2015-08-21 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cell Transformation, Neoplastic Genetics Epithelial Cells Metabolism Gene Expression Regulation, Neoplastic Intracellular Signaling Peptides And Proteins Prostate P21-Activated Kinases Actin-Related Protein 2-3 Complex Casein Kinase II Cell Line Cell Line, Tumor Pathology Epidermal Growth Factor Pharmacology Cytology Drug Effects Antagonists & Inhibitors Membrane Microdomains Phosphatidylinositol 3-Kinases Phosphorylation Protein Kinase Inhibitors Protein Transport RNA, Small Interfering Recombinant Proteins Signal Transduction Research Support, N.I.H., Extramural Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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