Murine c‐mpl: a member of the hematopoietic growth factor receptor superfamily that transduces a proliferative signal

• Published in: The EMBO journal 1993-07, Vol.12 (7), p.2645-2653
• Main Authors: Skoda, R.C., Seldin, D.C., Chiang, M.K., Peichel, C.L., Vogt, T.F., Leder, P.
• Format: Article
• Language: English
• Subjects: Alternative Splicing; Amino Acid Sequence; Animals; Base Sequence; Biological and medical sciences; Cells, Cultured; Chromosome Mapping; Cloning, Molecular; DNA; Fundamental and applied biological sciences. Psychology; Genes. Genome; Humans; Interleukin-4 - metabolism; Mice; Mice, Inbred C57BL; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Multigene Family; Neoplasm Proteins; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Receptors, Colony-Stimulating Factor - genetics; Receptors, Colony-Stimulating Factor - metabolism; Receptors, Cytokine; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; Receptors, Thrombopoietin; RNA, Messenger - genetics; Signal Transduction
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1002/j.1460-2075.1993.tb05925.x

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.