Tyrosine kinase activation through the extracellular domains of cytokine receptors.
Interaction of cytokines with their membrane receptors induces the proliferation and differentiation of a specific lineage of haematopoietic progenitors. The molecular mechanism of cytokine receptor-mediated signal transduction is unclear because these receptors do not have tyrosine kinase activity. Interleukin-3 and erythropoietin, however, induce transient tyrosine phosphorylation of a common set of proteins as a growth signal, and interleukin-2 induces phosphorylation of an overlapping but distinct set of proteins. Here we show that chimaeric receptors consisting of the extracellular domains of the erythropoietin receptor and the cytoplasmic domains of the interleukin-2 (or interleukin-3) receptor induce an erythropoietin-dependent tyrosine phosphorylation in interleukin-3-dependent Ba/F3 cells; however, chimaeric receptors composed of the extracellular domains of the interleukin-2 receptor and the cytoplasmic domains of the erythropoietin (or interleukin-3) receptor apparently transmit an interleukin-2-dependent signal. Our results indicate that these cytokines transmit distinct signals for activation of specific tyrosine kinases through the extracellular rather than cytoplasmic domains of the receptors.
Chiba
T
T
Tsukuba Life Science Center, Institute of Physical and Chemical Research (RIKEN), Ibaraki, Japan.
Nagata
Y
Y
Machide
M
M
Kishi
A
A
Amanuma
H
H
Sugiyama
M
M
Todokoro
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D001483:Base Sequence; D002478:Cells, Cultured; D004247:DNA; D004789:Enzyme Activation; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D017467:Receptors, Erythropoietin / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D016185:Receptors, Interleukin-3 / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism
D017467:Receptors, Erythropoietin; D015375:Receptors, Interleukin-2; D016185:Receptors, Interleukin-3; D011993:Recombinant Fusion Proteins; D014443:Tyrosine; D004247:DNA; D011505:Protein-Tyrosine Kinases