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Am J Physiol Heart Circ Physiol 290: H2509-H2515, 2006. First published December 22, 2005; doi:10.1152/ajpheart.00659.2005
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Nuclear compartmentalization of FAK and FRNK in cardiac myocytes

Xian Ping Yi,1,3,* Jibin Zhou,1,* Lu Huber,1 Jiaxiang Qu,1 Xuejun Wang,1 A. Martin Gerdes,1 and Faqian Li1,2

1Cardiovascular Research Institute-South Dakota Health Research Foundation, 2Department of Laboratory Medicine and Pathology, University of South Dakota School of Medicine, and Sioux Valley Hospitals and Health System, Sioux Falls, South Dakota; and 3Department of Pathology, Zhongshan University the Fifth Affiliated Hospital, Zhuhai, Guangdong Province, People's Republic of China

Submitted 20 June 2005 ; accepted in final form 20 December 2005

Focal adhesion kinase (FAK) and FAK-related non-kinase (FRNK) accumulate in the nucleus of cardiac myocytes during hypertensive hypertrophy. Nuclear FAK and FRNK are phosphorylated on different serines and form distinct bright spots. The subnuclear distribution of serine-phosphorylated FAK and FRNK was examined in this study by double labeling with fibrillarin, a component of nucleoli, and Sam68, a constituent of Sam68 nuclear bodies. We also investigated the role of protein kinase C (PKC)-mediated phosphorylation of FAK and FRNK on nuclear translocation. PKC activation by 12-O-tetradecanoylphorbol 13-acetate treatment increased serine phosphorylation of FAK and FRNK. Specifically, FAK was phosphorylated on serine 722 but not serine 910. On the other hand, FRNK was phosphorylated on serine 217, the equivalent site of FAK serine 910, but not serine 30, the homologous site of FAK serine 722. Serine-phosphorylated FAK and FRNK redistributed into the nucleus and formed distinct patterns. FAK with phosphorylation on serine 722 colocalized with Sam68 but not fibrillarin. On the contrary, FRNK phosphorylated on 217 coexisted with fibrillarin but not Sam68. Immunoprecipitation also confirmed that FAK associated with Sam68 and FRNK interacted with fibrillarin, respectively. These results suggest that FAK and FRNK target different nuclear subdomains by their association with distinct nuclear proteins.

focal adhesion kinase; focal adhesion kinase-related nonkinase; cardiac hypertrophy; hypertension; protein kinase C; nucleus



Address for reprint requests and other correspondence: F. Li, Cardiovascular Research Institute-South Dakota Health Research Foundation, 1100 East 21st St., Suite 700, Sioux Falls, SD 57105 (e-mail: fli{at}usd.edu)




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