INTERLEUKIN (IL)-2 AND IL-3 INDUCE DISTINCT BUT OVERLAPPING RESPONSESIN MURINE IL-3-DEPENDENT 32D CELLS TRANSDUCED WITH HUMAN IL-2 RECEPTOR BETA-CHAIN - INVOLVEMENT OF TYROSINE KINASE(S) OTHER THAN P56(LCK)

We have established IL-3-dependent 32D myeloid progenitor cells stably expressing the human IL-2 receptor beta-chain (IL-2R-beta). Whereas p arental 32D cells proliferated only in response to IL-3, the transduce d cells also proliferated in response to IL-2. Transduced cells expres sed high- and intermediate-affinity IL-2Rs, resulting from expression of human IL-2R-beta and murine IL-2R alpha-chain (IL-2R-alpha). IL-2 i nduced phenotypic changes not induced by IL-3, including the upregulat ed expression of endogenous murine IL-2R-alpha and IL-2R-beta and an i ncrease in cell size. Therefore, the transduced IL-2R-beta was not mer ely coupling with the IL-3 signaling pathway. IL-3 augmented several I L-2-induced responses including the up-regulation of IL-2R-alpha. Both IL-2- and IL-3-induced proliferation and IL-2 induced IL-2R-alpha exp ression were inhibited by the tyrosine kinase inhibitor herbimycin A. Thus, both IL-2- and IL-3-mediated effects required tyrosine kinase ac tivity. The identity of the tyrosine kinase(s) mediating the IL-2 sign als in these cells is not known but cannot be p56lck, a tyrosine kinas e found in T cells, since 32D-IL-2R-beta cells do not express p56lck.