THE ROLE OF MAP KINASE KINASE IN INTERLEUKIN-3 STIMULATION OF PROLIFERATION

Expression of a dominant interfering mutant of MAP kinase kinase (MAPK K) inhibits interleukin-3 (IL-3) activation of MAP kinase in the murin e bone marrow-derived cell line BAF3. This results in an increase in t he level of IL-3 required to stimulate cell proliferation and suppress apoptosis. When apoptosis is constitutively inhibited by coexpression of bcl-2, the dominant interfering MAPKK inhibits IL-3-driven cell cy cle progression. Thus, MAPKK function is necessary for optimal IL-3 in hibition of apoptosis and optimal IL-3 stimulation of entry into S pha se. Expression of a constitutively activated mutant of MAPKK does not replace IL-3, but renders cells able to proliferate in a density-depen dent manner. Cell contact is required to allow cell proliferation; suc h contact can be supplied by cells without activated MAPKK. (C) 1996 b y The American Society of Hematology.