INHIBITION OF CELL-GROWTH BY OVEREXPRESSION OF THE ZPK GENE

ZPK is a recently described serine/threonine protein kinase that is th ought to be involved in the regulation of cell proliferation and diffe rentiation. To directly determine whether ZPK exhibits any effect on c ell growth, NIH 3T3 fibroblasts were transfected with an expression ve ctor harboring the murine ZPK cDNA. Stable expression of this construc t led to a dramatic reduction in the proliferative capacity of these c ells as measured by a colony formation assay in monolayer culture. By contrast, overexpression of a ZPK cDNA with a mutation in the ATP-bind ing domain did not affect clonal expansion of the transfected cells. T hese findings suggest that the ZPK gene may act as a negative regulato r of cell growth and that this function may be mediated in part by the intrinsic kinase activity of the ZPK protein. (C) 1997 Academic Press .