Interleukin (IL)‐2 activation of p21^ras in murine myeloid cells transfected with human IL‐2 receptor β chain

The T cell growth factor interleukin‐2 (IL‐2) induces p21^ras activation in T lymphocytes. To determine whether the IL‐2 receptor (IL‐2R) can regulate p21^ras when expressed in a non‐T cell environment we have examined the ability of IL‐2 to activate p21^ras in 32D murine myeloid progenitor cells transduced with human IL‐2R β chains. These cells are denoted β53 cells. 32D cells normally proliferate in response to IL‐3 but the expression of the IL‐2R β chain confers IL‐2 responsiveness to the cells. Our data show that IL‐3 is able to activate p21^ras in the parental 32D cells and both IL‐2 and IL‐3 can stimulate p21^ras in the IL‐2R‐expressing β53 clone of 32D. In T lymphocytes, activation of protein kinase C (PKC) with phorbol esters is sufficient to stimulate p21^ras. However, in 32D and β53 cells activation of PKC with phorbol esters does not result in p21^ras activation even though these cells express functional PKC. It appears, therefore, that a PKC‐mediated pathway for p21^ras regulation exists in T lymphocytes but not in 32D cells. The IL‐2R can couple to p21^ras independently of the concomitant presence of the PKC pathway for p21^ras regulation. These data imply that multiple intracellular mechanisms may exist to regulate p21^ras and that cells of different lineages may differ with regard to p21^ras regulation.