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 bloodstream, They depart from this shape as part of the adhesion cascade by which they penetrate endothelium, interact with the extracellular matrix, and migrate through tissues, The mechanisms by which shape changes and altered adhesive properties are regulated are largely uncharacterized; however, they involve modulation of protein phosphorylation on tyrosine, Here, an inhibitor (MDHC) of protein tyrosine kinases (PTK) caused a shift in the morphology of a human T cell line from spherical to spread, This involved cytoskeletal components and was preceded by altered tyrosyl-phosphorylation and accompanied by an increased capacity for homotypic adhesion involving LFA-1 and CD2, Examples exist demonstrating 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 that MDHC accessed different steps in the adhesion cascade. (C) 1995 Academic Press, Inc.