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 p56lck.
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.
Otani
H
H
Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
Siegel
J P
JP
Erdos
M
M
Gnarra
J R
JR
Toledano
M B
MB
Sharon
M
M
Mostowski
H
H
Feinberg
M B
MB
Pierce
J H
JH
Leonard
W J
WJ
D000818:Animals; D016227:Benzoquinones; D002455:Cell Division; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D007377:Interleukin-3 / Q000502:physiology*; D047029:Lactams, Macrocyclic; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011809:Quinones / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000502:physiology*; D016185:Receptors, Interleukin-3 / Q000502:physiology; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction; D014162:Transfection; D015854:Up-Regulation
D016227:Benzoquinones; D007376:Interleukin-2; D007377:Interleukin-3; D047029:Lactams, Macrocyclic; D011518:Proto-Oncogene Proteins; D011809:Quinones; D015375:Receptors, Interleukin-2; D016185:Receptors, Interleukin-3; D017828:Rifabutin; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)