THE SCL GENE-PRODUCT IS REGULATED BY AND DIFFERENTIALLY REGULATES CYTOKINE RESPONSES DURING MYELOID LEUKEMIC-CELL DIFFERENTIATION

Differentiation induction in murine M1 leukemia cells by interleukin 6 (IL-6), leukemia inhibitory factor (LIF), and oncostatin M (OSM) is p ostulated to occur via a common receptor chain, gp130. In this study, growth factor-induced differentiation of M1 cells was accompanied by a late and persistent decrease in levels of mRNA and protein for a heli x-loop-helix transcription factor, the SCL gene product. To evaluate w hether reduced SCL expression was instrumental in monocyte differentia tion, an SCL cDNA expression vector was introduced into M1 cells to ob tain cell lines in which overexpression of SCL mRNA and protein was en forced. This resulted in a reduction in cells differentiating in respo nse to LIF and OSM but not in response to IL-6. Scatchard analysis ind icated that both parental and SCL-transfected cell lines exhibited sim ilar receptor numbers and receptor affinities for LIF, OSM, and IL-6, suggesting that the differential responsiveness was not due to selecti ve receptor down-modulation. Thus, these data implicate SCL in monocyt ic differentiation and provide evidence for differential receptor sign aling pathways despite utilization of a common gp130 subunit by all th ree receptors.