GROWTH FACTOR-MEDIATED K-1 CELL-PROLIFERATION( CHANNEL ACTIVITY ASSOCIATED WITH HUMAN MYELOBLASTIC ML)

ML-1 cell proliferation is dependent on the presence of serum growth f actors. Removing serum from the culture medium results in growth arres t and promotes differentiation. In this study, we found that a 4-amino pyridine-sensitive K+ channel was highly expressed in proliferating ML -1 cells and significantly diminished in G(1)-arrested ML-1 cells indu ced by serum deprivation but was restored within 30 min in these cells with addition of 10% fetal bovine serum (FBS) or 5 ng/ml epidermal gr owth factor (EGF). Intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels, but not guanosine 3',5'-cyclic monophosphate, were sign ificantly increased in serum-deprived cells stimulated by FBS or EGF, and the effects of FBS and EGF on the channel activation were mimicked by exogenous cAMP. In inside-out patches, K+ channel activity was sig nificantly increased by the cAMP-dependent protein kinase catalytic su bunit, whereas the effect of EGF on K+ channel activation was blocked by Rp-8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphothioate. Together, our results demonstrate that serum growth factors stimulate K+ channel activity in proliferation of ML-1 cells through protein ki nase-induced phosphorylation and suggest an important molecular mechan ism for serum growth factor-stimulated mitogenesis in ML-1 cells.