ARHGAP21 associates with FAK and PKCzeta and is redistributed after cardiac pressure overload.
Biochem Biophys Res Commun
; 374(4): 641-6, 2008 Oct 03.
Article
em En
| MEDLINE
| ID: mdl-18662671
ABSTRACT
ARHGAP21 is highly expressed in the heart, which demonstrates activity over Cdc42 and interacts with proteins of the cytoskeleton and adherent junctions. The main cause of cardiac hypertrophy is mechanical stimulus; therefore we analyzed ARHGAP21 expression after acute mechanical stress in the myocardium and its association with FAK and PKCzeta. We demonstrated that ARHGAP21 is relocated to Z-lines and costameres after pressure overload, and interacts with PKCzeta and FAK in control rats (sham), rats submitted to aortic clamping and spontaneously hypertensive rats (SHR). Co-transfection using ARHGAP21 and PKCzeta constructions demonstrated that ARHGAP21 associates with PKCzeta-GST and endogenous FAK. Pulldown assay showed that ARHGAP21 binds to the C-terminal region of FAK. Moreover, ARHGAP21 binds to PKCzeta phosphorylated on Thr410 in sham and SHR. However, ARHGAP21 only binds to FAK phosphorylated on Tyr925 of SHR. Additionally, PKCzeta is phosphorylated by mechanical stimuli. These results suggest that ARHGAP21 may act as a signaling or scaffold protein of FAK and PKCzeta signaling pathways, developing an important function during cardiac stress.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Hipertrofia Ventricular Esquerda
/
Chaperonas Moleculares
/
Proteínas Adaptadoras de Transdução de Sinal
/
Quinase 1 de Adesão Focal
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Brasil