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Title: Comparative analysis of the role of small G proteins in cell migration and cell death: Cytoprotective and promigratory effects of RalA

Journal Article · · Experimental Cell Research
; ;  [1];  [2]; ;  [3];  [4];  [5];  [1]
  1. Department of Pharmacology, Brain Science and Engineering Institute, Kyungpook National University School of Medicine, Daegu (Korea, Republic of)
  2. School of Life Sciences and Biotechnology, Kyungpook National University, Daegu (Korea, Republic of)
  3. Department of Physiology, Institute of Health Science, Gyeongsang National University School of Medicine, Jinju (Korea, Republic of)
  4. Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon (Korea, Republic of)
  5. Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

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.

OSTI ID:
22212165
Journal Information:
Experimental Cell Research, Vol. 317, Issue 14; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
Country of Publication:
United States
Language:
English

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