INTERLEUKIN (IL)-2 AND IL-3 INDUCE DISTINCT BUT OVERLAPPING RESPONSES IN 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 parental 32D cells proliferated only in response to IL-3, the transduced cells also proliferated in response to IL-2. Transduced cells expressed 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 induced phenotypic changes not induced by IL-3, including the upregulated expression of endogenous murine IL-2R-alpha and IL-2R-beta and an increase in cell size. Therefore, the transduced IL-2R-beta was not merely coupling with the IL-3 signaling pathway. IL-3 augmented several IL-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 expression were inhibited by the tyrosine kinase inhibitor herbimycin A. Thus, both IL-2- and IL-3-mediated effects required tyrosine kinase activity. The identity of the tyrosine kinase(s) mediating the IL-2 signals in these cells is not known but cannot be p56lck, a tyrosine kinase found in T cells, since 32D-IL-2R-beta cells do not express p56lck.