Cytoplasmic domains of the interleukin-2 receptor beta and gamma chains mediate the signal for T-cell proliferation.
The interleukin-2 receptor (IL-2R) consists of three distinct chains (alpha, beta, gamma) which bind IL-2 and generate a proliferative signal in T cells. To define the mechanism of receptor activation, chimaeric receptors were constructed from the intracellular region of either IL-2R beta or IL-2R gamma and the extracellular region of c-kit, a receptor tyrosine kinase that homodimerizes on binding stem cell factor (SCF). We report here that binding of SCF to the beta-chain chimaera induced proliferation of the pro-B-cell line BA/F3, but not T cells. But in T cells expressing both the beta- and gamma-chain chimaeras, SCF induced proliferation and tyrosine phosphorylation characteristic of the native IL-2R signal. Chimaeric IL-2 receptor beta and gamma chains constructed with the heterodimeric extracellular regions of the granulocyte-macrophage colony stimulating factor receptor (GM-CSFR) also provided the IL-2R signal. Thus, heterodimerization of the cytoplasmic domains of IL-2R beta and -gamma appears necessary and sufficient for signalling in T cells.
Nelson
B H
BH
Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Lord
J D
JD
Greenberg
P D
PD
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D001483:Base Sequence; D001704:Biopolymers; D002460:Cell Line; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D016298:Hematopoietic Cell Growth Factors / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000502:physiology; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D016184:Receptors, Colony-Stimulating Factor / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000737:chemistry* / Q000502:physiology*; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction / Q000276:immunology*; D019089:Stem Cell Factor; D013601:T-Lymphocytes / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism
D001704:Biopolymers; D016298:Hematopoietic Cell Growth Factors; D011518:Proto-Oncogene Proteins; D016184:Receptors, Colony-Stimulating Factor; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D019089:Stem Cell Factor; D014443:Tyrosine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases