INCREASE IN RECEPTOR-LIKE PROTEIN-TYROSINE-PHOSPHATASE ACTIVITY AND EXPRESSION LEVEL ON DENSITY-DEPENDENT GROWTH ARREST OF ENDOTHELIAL-CELLS

Protein tyrosine phosphatase (PTPase) activity was examined in two cel l lines: human umbilical vein endothelial (HUVE) cells, which display contact inhibition of cell growth, and A427 human adenocarcinoma cells , which have lost this ability. HUVE cells harvested at high density d isplayed a 10-fold increase in membrane-associated PTPase activity. A4 27 cells exhibited no such phenomenon. Moreover, modification of HUVE cell growth rate by a stimulating agent such as basic fibroblast growt h factor or by blocking compounds such as thymidine or suramin resulte d in no change in PTPase activity, suggesting that the observed increa se in membrane-associated activity at confluency was specific for cell -cell-contact-directed growth arrest. The expression of various PTPase mRNAs was examined in HUVE and A427 cells. Of the receptor-like PTPas es tested, two were exclusively expressed in HUVE cells (PTP gamma and HPTP beta). Only HPTP beta, which is structurally similar in its extr acellular region to cell-adhesion receptors of the immunoglobulin supe rfamily, displayed a pattern of expression related to the increase in PTPase activity. Competitive PCR was used to quantify its expression d uring cell culture. A 12-fold increase in HPTP beta mRNA expression wa s detected and it parallelled the time course of PTPase activity. This observation strongly implicates receptorlike PTPases in density-depen dent growth arrest.