Forced engagement of c-Kit and Flt-3 induces Ba/F3 cell proliferation.

The effects of different CIDs on representative Ba/F3 cell clones expressing various combinations of the dimerizable fusion proteins were tested in transient cell-proliferation assays using FK1012 (upper panels), AP1510 (middle panels), or rapamycin (lower panels). The degree of proliferation is indicated as a fraction of that obtained using 5% of IL-3–containing WEHI-3–conditioned medium, which induces more than 50% of maximal IL-3–dependent cell growth.3 Each line depicts a different cell clone. (A) Ba/F3 cells expressing the c-Kit^3FKBP12 fusion proliferate in response to FK1012 and AP1510, but fail to proliferate in the presence of rapamycin. (B) Clones coexpressing c-Kit^3FKBP12and c-Kit^3FRB proliferate in response to FK1012, but also proliferate in response to rapamycin. (C) Ba/F3 cells expressing both the c-Kit^3FKBP12 and the Flt-3^3FRB fusions exhibit proliferative responses to FK1012, AP1510, and rapamycin. (D) Likewise, clones coexpressing c-Kit^1FKBP12 and Flt-3^1FRB were capable of responding to all 3 drugs, with the effects of rapamycin indicating that heterodimerization of c-Kit and Flt-3 can induce cell growth.