Murine c-mpl: a member of the hematopoietic growth factor receptor superfamily that transduces a proliferative signal.
The murine myeloproliferative leukemia virus has previously been shown to contain a fragment of the coding region of the c-mpl gene, a member of the cytokine receptor superfamily. We have isolated cDNA and genomic clones encoding murine c-mpl and localized the c-mpl gene to mouse chromosome 4. Since some members of this superfamily function by transducing a proliferative signal and since the putative ligand of mpl is unknown, we have generated a chimeric receptor to test the functional potential of mpl. The chimera consists of the extracellular domain of the human interleukin-4 receptor and the cytoplasmic domain of mpl. A mouse hematopoietic cell line transfected with this construct proliferates in response to human interleukin-4, thereby demonstrating that the cytoplasmic domain of mpl contains all elements necessary to transmit a growth stimulatory signal. In addition, we show that 25-40% of mpl mRNA found in the spleen corresponds to a novel truncated and potentially soluble isoform of mpl and that both full-length and truncated forms of mpl protein can be immunoprecipitated from lysates of transfected COS cells. Interestingly, however, although the truncated form of the receptor possesses a functional signal sequence and lacks a transmembrane domain, it is not detected in the culture media of transfected cells.
Skoda
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RC
Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115.
Seldin
D C
DC
Chiang
M K
MK
Peichel
C L
CL
Vogt
T F
TF
Leder
P
P
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004247:DNA; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D005810:Multigene Family; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D016184:Receptors, Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D053628:Receptors, Thrombopoietin; D015398:Signal Transduction
D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016184:Receptors, Colony-Stimulating Factor; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D015847:Interleukin-4; D004247:DNA