INVOLVEMENT OF PROTEIN-TYROSINE KINASES IN REGULATION OF ENDOTHELIAL-CELL ORGANIZATION BY BASEMENT-MEMBRANE PROTEINS

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.