ZAK negatively regulates RhoGDIbeta-induced Rac1-mediated hypertrophic growth and cell migration.
RhoGDIbeta, a Rho GDP dissociation inhibitor, induced hypertrophic growth and cell migration in a cultured cardiomyoblast cell line, H9c2. We demonstrated that RhoGDIbeta 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 RhoGDIbeta expression by RNA interference blocked RhoGDIbeta-induced Rac1 expression and cell migration. We demonstrated that the co-expression of ZAK and RhoGDIbeta in cells resulted in an inhibition in the activity of ZAK to induce ANF expression. Knockdown of ZAK expression in ZAK-RhoGDIbeta-expressing cells by ZAK-specific RNA interference restored the activities of RhoGDIbeta.
Huang
Chih-Yang
CY
Graduate Institute of Chinese Medical Science, China Medical University, Taichung 404, Taiwan. cyhuang@mail.cmu.edu.tw
Yang
Li-Chiu
LC
Liu
Kuan-Yu
KY
Chang
I-Chang
IC
Liao
Pao-Hsin
PH
Chou
Janet Ing-Yuh
JI
Chou
Ming-Yung
MY
Lin
Wei-Wen
WW
Yang
Jaw-Ji
JJ
D000818:Animals; D049108:Cell Enlargement; D002465:Cell Movement; D002478:Cells, Cultured; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000235:genetics / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D014162:Transfection; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
D020730:Guanine Nucleotide Dissociation Inhibitors; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D011494:Protein Kinases; D020830:rac1 GTP-Binding Protein