M. Lobo et I. Zachary, Nuclear localization and apoptotic regulation of an amino-terminal domain focal adhesion kinase fragment in endothelial cells, BIOC BIOP R, 276(3), 2000, pp. 1068-1074
Citations number
36
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
This study investigated the subcellular compartmentalization of focal adhes
ion kinase (FAK) fragments and their regulation during apoptosis of human u
mbilical vein endothelial cells. A 50 kDa NH2-terminal FAK fragment and a 1
20 kDa FAB variant were constitutively expressed and specifically found in
the nuclear fraction of cells, while a 55 kDa COOH-terminal FAK fragment wa
s only in the cytosolic fraction, FAK cleavage fragments generated during a
poptosis remained in the cytosol, while p120FAK and p50 NH2-terminal FAK re
mained in the nuclear compartment, The caspase inhibitor, ZVAD-fmk, prevent
ed the apoptosis-induced proteolysis of p125 and p120FAK, generation of the
80 kDa cleavage product, and increased expression of p50N-FAK. Western blo
t with phospho-specific FAB: showed that nuclear p125(FAK) was phosphorylat
ed at a significant level at Y861, while FAB phosphorylated at Y397 and Y40
7 was largely in the cytosol. These results indicate that FAK NH2- and COOH
-terminal domain fragments are segregated between nuclear and cytosolic com
partments in endothelial cells and suggest novel functions for the FAK NH2-
terminal domain. (C) 2000 Academic Press.