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

Hyejin Jeon, Long Tai Zheng, Shinrye Lee, Won Ha Lee, Nammi Park, Jae Yong Park, Won Do Heo, Myung Shik Lee, Kyoungho Suk

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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.

Original languageEnglish
Pages (from-to)2007-2018
Number of pages12
JournalExperimental Cell Research
Volume317
Issue number14
DOIs
StatePublished - 15 Aug 2011

Keywords

  • Apoptosis
  • Cell death
  • Cell migration
  • RalA
  • Small G protein

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