Ligand-dependent activation of chimeric receptors with the cytoplasmic domain of the interleukin-3 receptor beta subunit (beta IL3).
beta IL3 (formerly known as AIC2A), a beta subunit of the murine interleukin-3 receptor (IL-3R), is not only required for formation of the high affinity receptor but is also important for signal transduction. To examine the function of beta IL3 in signal transduction, we constructed several chimeric receptors consisting of the intracellular portion of beta IL3 and the extracellular portion of other members of the cytokine receptor superfamily, i.e. the human interleukin-2 receptor beta chain (hIL-2R beta), the human interleukin-4 receptor (hIL-4R), and the murine erythropoietin receptor (mEpoR). These chimeric receptors and normal cytokine receptors were expressed in an IL-3-dependent murine pro-B cell line, Ba/F3, and an IL-2-dependent murine T cell line, CTLL2. Regardless of the origin of the extracellular domain, these chimeric receptors were functional in Ba/F3 cells; they stimulated proliferation and induced tyrosine phosphorylation in response to the cytokine corresponding to the extracellular domain. However, the response of transfectants expressing chimeric receptors was similar to, but not identical with, the response of Ba/F3 cells to mIL-3. We present evidence that the IL-4R and EpoR probably have an additional component which is involved in signal transduction.
Sakamaki
K
K
Department of Molecular Biology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304.
Wang
H M
HM
Miyajima
I
I
Kitamura
T
T
Todokoro
K
K
Harada
N
N
Miyajima
A
A
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D007377:Interleukin-3 / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D017467:Receptors, Erythropoietin / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D016185:Receptors, Interleukin-3 / Q000737:chemistry / Q000378:metabolism*; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction
D002352:Carrier Proteins; D007377:Interleukin-3; D017467:Receptors, Erythropoietin; D015375:Receptors, Interleukin-2; D016185:Receptors, Interleukin-3; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D011993:Recombinant Fusion Proteins; C072185:Csf2rb2 protein, mouse; D015847:Interleukin-4