title: Comparative analysis of the role of small G proteins in cell migration and cell death: cytoprotective and promigratory effects of RalA.
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.
authors.affiliation: Department of Pharmacology, Brain Science and Engineering Institute, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Hyejin
authors.initials: H
authors.lastname: Jeon
authors.forename: Long Tai
authors.initials: LT
authors.lastname: Zheng
authors.forename: Shinrye
authors.initials: S
authors.lastname: Lee
authors.forename: Won-Ha
authors.initials: WH
authors.lastname: Lee
authors.forename: Nammi
authors.initials: N
authors.lastname: Park
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Park
authors.forename: Won Do
authors.initials: WD
authors.lastname: Heo
authors.forename: Myung-Shik
authors.initials: MS
authors.lastname: Lee
authors.forename: Kyoungho
authors.initials: K
authors.lastname: Suk
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D016923:Cell Death; D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020725:ral GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C492198:RALA protein, human; D020559:Monomeric GTP-Binding Proteins; D020725:ral GTP-Binding Proteins