ALTERING THE EXPRESSION OF CELL-SURFACE BETA-1, 4-GALACTOSYLTRANSFERASE MODULATES CELL-GROWTH

beta 1,4-Galactosyltransferase (GalTase) is unusual among the glycosyl transferases in that it is localized both in the Golgi complex and on the cell surface. Most studies of surface GalTase function have focuse d on its role in cellular interactions; however, surface GalTase has a lso been suggested to function during cellular proliferation. Consiste nt with this hypothesis, a variety of GalTase-specific perturbants inh ibit cell growth in vitro and in vivo. However, all of these studies h ave been limited to the use of exogenous reagents to perturb GalTase f unction. Furthermore, all of these perturbants inhibit cell growth, ir respective of whether they stimulate or inhibit GalTase enzyme activit y. Therefore, it remains unclear whether surface GalTase delivers a gr owth inhibitory or growth stimulatory signal. in this study, we took a more direct approach to defining surface GalTase function during grow th by examining its expression during the cell cycle and by molecularl y altering its expression in stably transfected cell lines. The expres sion of GalTase was shown to be cell cycle specific, with the cell sur face and intracellular GalTase pools displaying independent expression patterns. Furthermore, multiple, independent, stably transfected cell Lines with reduced levels of cytoskeletally associated surface GalTas e grew faster than control cells, whereas cell lines that overexpresse d surface GalTase grew slower than controls. These observations direct ly support the concept that surface GalTase delivers a growth inhibito ry signal. Evidence is presented suggesting that surface GalTase inter acts with the epidermal growth factor (EGF) receptor, as suggested by others. The activity of the EGF receptor was shown to be directly prop ortional to the growth rate of the various GalTase-transfected cell li nes. Thus, the expression of surface GalTase directly affects cell pro liferation rate and may do so by modulating the ability of the EGF rec eptor to transduce EGF-dependent signals. (C) 1995 Academic Press, Inc .