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 membe r of the cytokine receptor superfamily. We have isolated cDNA and geno mic clones encoding murine c-mpl and localized the c-mpl gene to mouse chromosome 4. Since some members of this superfamily function by tran sducing 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 prolife rates in response to human interleukin-4, thereby demonstrating that t he cytoplasmic domain of mpl contains all elements necessary to transm it a growth stimulatory signal. In addition, we show that 25-40% of mp l mRNA found in the spleen corresponds to a novel truncated and potent ially soluble isoform of mpl and that both full-length and truncated f orms of mpl protein can be immunoprecipitated from lysates of transfec ted COS cells. Interestingly, however, although the truncated form of the receptor possesses a functional signal sequence and tacks a transm embrane domain, it is not detected in the culture media of transfected cells.