Interleukin (IL)-2 activation of p21ras in murine myeloid cells transfected with human IL-2 receptor beta chain.
The T cell growth factor interleukin-2 (IL-2) induces p21ras activation in T lymphocytes. To determine whether the IL-2 receptor (IL-2R) can regulate p21ras when expressed in a non-T cell environment we have examined the ability of IL-2 to activate p21ras in 32D murine myeloid progenitor cells transduced with human IL-2R beta chains. These cells are denoted beta 53 cells. 32D cells normally proliferate in response to IL-3 but the expression of the IL-2R beta chain confers IL-2 responsiveness to the cells. Our data show that IL-3 is able to activate p21ras in the parental 32D cells and both IL-2 and IL-3 can stimulate p21ras in the IL-2R-expressing beta 53 clone of 32D. In T lymphocytes, activation of protein kinase C (PKC) with phorbol esters is sufficient to stimulate p21ras. However, in 32D and beta 53 cells activation of PKC with phorbol esters does not result in p21ras activation even though these cells express functional PKC. It appears, therefore, that a PKC-mediated pathway for p21ras regulation exists in T lymphocytes but not in 32D cells. The IL-2R can couple to p21ras independently of the concomitant presence of the PKC pathway for p21ras regulation. These data imply that multiple intracellular mechanisms may exist to regulate p21ras and that cells of different lineages may differ with regard to p21ras regulation.
Izquierdo
M
M
Lymphocyte Activation Laboratory, Imperial Cancer Research Fund, London, GB.
Downward
J
J
Otani
H
H
Leonard
W J
WJ
Cantrell
D A
DA
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000737:chemistry; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology; D051379:Mice; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D016283:Proto-Oncogene Proteins p21(ras) / Q000032:analysis*; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000502:physiology*; D014162:Transfection
D007376:Interleukin-2; D007377:Interleukin-3; D015375:Receptors, Interleukin-2; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)