Subcellular redistribution of focal adhesion kinase and its related nonkinase in hypertrophic myocardium.
Focal adhesion kinase (FAK) and focal adhesion kinase-related nonkinase (FRNK) are likely involved in mechanical signaling during hypertension. We investigated expression, subcellular distribution, and phosphorylation of FAK, as well as FRNK in left ventricles of spontaneously hypertensive heart failure rats. Compared with normotensive controls, FAK and FRNK increased in left ventricles of hypertensive rats. Increased FAK and FRNK were mainly present in membrane cytoskeleton and nuclear fractions. Confocal microscopy demonstrated that FAK and FRNK translocated to nuclei and intercalated disks in cardiac myocytes from hypertensive rats. Serine and tyrosine phosphorylation of FAK increased dramatically in hypertensive rats. FAK phosphorylated at tyrosine 397 was present in membranes and intercalated disks, but not in nuclei. FAK was also phosphorylated on serine 722 but not on serine 910. In contrast, FRNK was phosphorylated on serine 217, the equivalent site of FAK serine 910, but not serine on 30, the homologous site of FAK serine 722. Serine phosphorylated FAK and FRNK accumulated in membranes and nuclei but not in intercalated disks. Nuclear translocation of FAK and FRNK may play important roles in regulating mechanical signal transduction in cardiac myocytes.
South Dakota Health Research Foundation-Cardiovascular Research Institute, 1400 W 22nd St, Sioux Falls, SD 57105, USA.
Xian Ping
XP
Yi
Xuejun
X
Wang
A Martin
AM
Gerdes
Faqian
F
Li
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D002467:Cell Nucleus / Q000201:enzymology; D003599:Cytoskeleton / Q000201:enzymology; D005260:Female; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006333:Heart Failure / Q000201:enzymology; D006352:Heart Ventricles / Q000201:enzymology; D006973:Hypertension / Q000201:enzymology*; D017379:Hypertrophy, Left Ventricular / Q000201:enzymology*; D032383:Myocytes, Cardiac / Q000201:enzymology; D010766:Phosphorylation; D021381:Protein Transport; D011505:Protein-Tyrosine Kinases / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012694:Serine / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D014443:Tyrosine; D012694:Serine; C113183:FAK-related nonkinase; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496052:Ptk2 protein, rat