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RhoGDIbeta-induced hypertrophic growth in H9c2 cells is negatively regulated by ZAK.


ABSTRACT: We found that overexpression of RhoGDIbeta, a Rho GDP dissociation inhibitor, induced hypertrophic growth and suppressed cell cycle progression in a cultured cardiomyoblast cell line. Knockdown of RhoGDIbeta expression by RNA interference blocked hypertrophic growth. We further demonstrated that RhoGDIbeta physically interacts with ZAK and is phosphorylated by ZAK in vitro, and this phosphorylation negatively regulates RhoGDIbeta functions. Moreover, the ZAK-RhoGDIbeta interaction may maintain ZAK in an inactive hypophosphorylated form. These two proteins could negatively regulate one another such that ZAK suppresses RhoGDIbeta functions through phosphorylation and RhoGDIbeta counteracts the effects of ZAK by physical interaction. Knockdown of ZAK expression in ZAK- and RhoGDIbeta-expressing cells by ZAK-specific RNA interference restored the full functions of RhoGDIbeta.

SUBMITTER: Huang CY 

PROVIDER: S-EPMC2653512 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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RhoGDIbeta-induced hypertrophic growth in H9c2 cells is negatively regulated by ZAK.

Huang Chih-Yang CY   Yang Li-Chiu LC   Liu Kuan-Yu KY   Liao Pao-Hsin PH   Chou Janet Ing-Yuh JI   Chou Ming-Yung MY   Lin Wei-Wen WW   Yang Jaw-Ji JJ  

Journal of biomedical science 20090122


We found that overexpression of RhoGDIbeta, a Rho GDP dissociation inhibitor, induced hypertrophic growth and suppressed cell cycle progression in a cultured cardiomyoblast cell line. Knockdown of RhoGDIbeta expression by RNA interference blocked hypertrophic growth. We further demonstrated that RhoGDIbeta physically interacts with ZAK and is phosphorylated by ZAK in vitro, and this phosphorylation negatively regulates RhoGDIbeta functions. Moreover, the ZAK-RhoGDIbeta interaction may maintain Z  ...[more]

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