ZAK negatively regulates RhoGDIβ-induced Rac1-mediated hypertrophic growth and cell migration

doi:10.1186/1423-0127-16-56

Journal of Biomedical Science

Volume 16

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Research

ZAK negatively regulates RhoGDIβ-induced Rac1-mediated hypertrophic growth and cell migration

Chih-Yang Huang¹^,2^,3^* , Li-Chiu Yang⁴^,5^,6^* , Kuan-Yu Liu⁴^* , I-Chang Chang⁷ , Pao-Hsin Liao⁴^,6 , Janet Ing-Yuh Chou⁸ , Ming-Yung Chou⁴^,6 , Wei-Wen Lin⁹ and Jaw-Ji Yang⁴

¹Graduate Institute of Chinese Medical Science, China Medical University, Taichung 404, Taiwan

²Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan

³Department of Health and Nutrition Biotechnology, Asia University, Taichung 413, Taiwan

⁴School of Dentistry, Chung-Shan Medical University, Taichung 402, Taiwan

⁵Institute of Medicine, Chung-Shan Medical University, Taichung 402, Taiwan

⁶Chung-Shan Medical University Hospital, Chung-Shan Medical University, Taichung 402, Taiwan

⁷Department of Orthopedics Surgery, Chung-Shan Medical University, Taichung 402, Taiwan

⁸Midwestern University Chicago College of Osteopathic Medicine, Chicago, USA

⁹Cardiovascular Center, Veterans General Hospital, Taichung 407, Taiwan

author email corresponding author email* Contributed equally

Journal of Biomedical Science 2009, 16:56doi:10.1186/1423-0127-16-56


Published:	18 June 2009

Abstract

RhoGDIβ, a Rho GDP dissociation inhibitor, induced hypertrophic growth and cell migration in a cultured cardiomyoblast cell line, H9c2. We demonstrated that RhoGDIβ plays a previously undefined role in regulating Rac1 expression through transcription to induce hypertrophic growth and cell migration and that these functions are blocked by the expression of a dominant-negative form of Rac1. We also demonstrated that knockdown of RhoGDIβ expression by RNA interference blocked RhoGDIβ-induced Rac1 expression and cell migration. We demonstrated that the co-expression of ZAK and RhoGDIβ in cells resulted in an inhibition in the activity of ZAK to induce ANF expression. Knockdown of ZAK expression in ZAK-RhoGDIβ-expressing cells by ZAK-specific RNA interference restored the activities of RhoGDIβ.