ARHGAP21 associates with FAK and PKCzeta and is redistributed after cardiac pressure overload.
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.
Borges
Luciene
L
Department of Internal Medicine, Hematology and Hemotherapy Center, School of Medical Science, University of Campinas-UNICAMP, Campinas, São Paulo 13083-970, Brazil.
Bigarella
Carolina Louzão
CL
Baratti
Mariana Ozello
MO
Crosara-Alberto
Daniella P
DP
Joazeiro
Paulo P
PP
Franchini
Kleber G
KG
Costa
Fernando F
FF
Saad
Sara Teresinha Olalla
ST
D021581:Active Transport, Cell Nucleus; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus; D004195:Disease Models, Animal; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D017379:Hypertrophy, Left Ventricular / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000648:ultrastructure; D010766:Phosphorylation; D011312:Pressure; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D000099221:Protein Kinase C zeta
D048868:Adaptor Proteins, Signal Transducing; D051417:Focal Adhesion Kinase 1; D018832:Molecular Chaperones; C531247:Arhgap21 protein, rat; C490392:Prkcz protein, rat; D000099221:Protein Kinase C zeta; C496052:Ptk2 protein, rat