RhoGDIbeta-induced hypertrophic growth in H9c2 cells is negatively regulated by ZAK.
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.
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
Liao
Pao-Hsin
PH
Chou
Janet Ing-Yuh
JI
Chou
Ming-Yung
MY
Lin
Wei-Wen
WW
Yang
Jaw-Ji
JJ
D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006984:Hypertrophy / Q000378:metabolism* / Q000473:pathology; D016350:Leucine Zippers; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
D020730:Guanine Nucleotide Dissociation Inhibitors; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D017346:Protein Serine-Threonine Kinases