MODULATION OF T-CELL MORPHOLOGY AND INDUCTION OF HOMOTYPIC ADHESION BY A PROTEIN-TYROSINE KINASE INHIBITOR

T cells are spherical in culture and during travel through the bloodst ream, They depart from this shape as part of the adhesion cascade by w hich they penetrate endothelium, interact with the extracellular matri x, and migrate through tissues, The mechanisms by which shape changes and altered adhesive properties are regulated are largely uncharacteri zed; however, they involve modulation of protein phosphorylation on ty rosine, Here, an inhibitor (MDHC) of protein tyrosine kinases (PTK) ca used a shift in the morphology of a human T cell line from spherical t o spread, This involved cytoskeletal components and was preceded by al tered tyrosyl-phosphorylation and accompanied by an increased capacity for homotypic adhesion involving LFA-1 and CD2, Examples exist demons trating prevention of morphological alteration or cell adhesion by PTK inhibitors, and thus MDHC differed from these other inhibitors. This suggests differential sites of action for PTK inhibitors and perhaps t hat MDHC accessed different steps in the adhesion cascade. (C) 1995 Ac ademic Press, Inc.