TY - JOUR
T1 - Comparative analysis of the role of small G proteins in cell migration and cell death
T2 - Cytoprotective and promigratory effects of RalA
AU - Jeon, Hyejin
AU - Zheng, Long Tai
AU - Lee, Shinrye
AU - Lee, Won Ha
AU - Park, Nammi
AU - Park, Jae Yong
AU - Heo, Won Do
AU - Lee, Myung Shik
AU - Suk, Kyoungho
PY - 2011/8/15
Y1 - 2011/8/15
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Cell death
KW - Cell migration
KW - RalA
KW - Small G protein
UR - http://www.scopus.com/inward/record.url?scp=79960102252&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2011.05.021
DO - 10.1016/j.yexcr.2011.05.021
M3 - Article
AN - SCOPUS:79960102252
SN - 0014-4827
VL - 317
SP - 2007
EP - 2018
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 14
ER -