Comparative analysis of the role of small G proteins in cell migration and cell death: cytoprotective and promigratory effects of RalA |
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Authors: | Jeon Hyejin Zheng Long Tai Lee Shinrye Lee Won-Ha Park Nammi Park Jae-Yong Heo Won Do Lee Myung-Shik Suk Kyoungho |
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Institution: | aDepartment of Pharmacology, Brain Science and Engineering Institute, Kyungpook National University School of Medicine, Daegu, Republic of Korea;bSchool of Life Sciences and Biotechnology, Kyungpook National University, Daegu, Republic of Korea;cDepartment of Physiology, Institute of Health Science, Gyeongsang National University School of Medicine, Jinju, Republic of Korea;dDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea;eDepartment of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea |
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Abstract: | Small G protein superfamily consists of more than 150 members, and is classified into six families: the Ras, Rho, Rab, Arf, Ran, and RGK families. They regulate a wide variety of cell functions such as cell proliferation/differentiation, cytoskeletal reorganization, vesicle trafficking, nucleocytoplasmic transport and microtubule organization. The small G proteins have also been shown to regulate cell death/survival and cell shape. In this study, we compared the role of representative members of the six families of small G proteins in cell migration and cell death/survival, two cellular phenotypes that are associated with inflammation, tumorigenesis, and metastasis. Our results show that small G proteins of the six families differentially regulate cell death and cell cycle distribution. In particular, our results indicate that Rho family of small G proteins is antiapoptotic. Ras, Rho, and Ran families promoted cell migration. There was no significant correlation between the cell death- and cell migration-regulating activities of the small G proteins. Nevertheless, RalA was not only cytoprotective against multiple chemotherapeutic drugs, but also promigratory inducing stress fiber formation, which was accompanied by the activation of Akt and Erk pathways. Our study provides a framework for further systematic investigation of small G proteins in the perspectives of cell death/survival and motility in inflammation and cancer. |
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Keywords: | Small G protein Cell death Apoptosis Cell migration RalA |
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