DISTINCT CYTOPLASMIC REGIONS OF THE HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR-RECEPTOR INVOLVED IN INDUCTION OF PROLIFERATION AND MATURATION

The granulocyte colony-stimulating factor receptor (G-CSF-R) transduce s signals important for the proliferation and maturation of myeloid pr ogenitor cells. To identify functionally important regions in the cyto plasmic domain of the G-CSF-R, we compared the actions of the wild-typ e receptor, two mutants, and a natural splice variant in transfectants of the mouse pro-B cell line BAF3 and two myeloid cell lines, 32D and L-GM. A region of 55 amino acids adjacent to the transmembrane domain was found to be sufficient for generating a growth signal. The immedi ate downstream sequence of 30 amino acids substantially enhanced the g rowth signaling in the three cell lines. In contrast, the carboxy-term inal part of 98 amino acids strongly inhibited growth signaling in the two myeloid cell lines but not in BAF3 cells. Truncation of this regi on lead to an inability of the G-CSF-R to transduce maturation signals in L-GM cells. An alternative carboxy tail present in a splice varian t of the G-CSF-R also inhibited growth signaling, notably in both the myeloid cells and BAF3 cells, but appeared not to be involved in matur ation.