Gm. Williams et al., INVOLVEMENT OF PROTEIN-TYROSINE KINASES IN REGULATION OF ENDOTHELIAL-CELL ORGANIZATION BY BASEMENT-MEMBRANE PROTEINS, Biochemical and biophysical research communications, 229(2), 1996, pp. 375-380
During capillary formation, endothelial cell migration and organizatio
n are critically dependent on surrounding basement membrane proteins.
These proteins serve as a physical support and are likely to provide s
ignals which regulate migration and organization of the cells. In this
study the possible involvement of a tyrosine kinase signalling pathwa
ys in basement membrane-induced organization of human endothelial cell
s is examined. Interaction of endothelial cells with reconstituted bas
ement membrane Matrigel activates tyrosine phosphorylation of several
proteins including focal adhesion kinase. Inhibition of this pathway w
ith tyrosine kinase inhibitors impairs localization of paxillin to foc
al adhesions and organization of actin filaments, decreases motility a
nd elongation of endothelial cells, and prevents their organization in
to cords or tubes on basement membrane. These data demonstrate that ba
sement membrane-induced modulation of endothelial cell motility, shape
, and organization is critically dependent on tyrosine kinase signalli
ng pathway(s) involving cytoskeletal proteins. (C) 1996 Academic Press
, Inc.