Specific expression of heterotrimeric G proteins G12 and G16 during human myeloid differentiation.

To evaluate expression of heterotrimeric guanosine triphosphate (GTP)-binding proteins (G proteins) in human myeloid cells, we studied expression at the protein level of their alpha subunits (G alpha, the subunits responsible for the name and specificity of G proteins) in normal human myeloid progenitors and mature blood cells. We found that G alpha(s), G alpha(i2), and G alpha(q/11) proteins were expressed at high levels at all stages of granulomonocytic and erythroid differentiation, whereas expression of G alpha12 and G alpha16 proteins in normal myeloid cells was lineage-specific. G alpha12 proteins were expressed in erythroid progenitors, monocytes, and platelets, but not in normal granulocytic cells. This lineage specificity was lost in leukemic cells: G alpha12 proteins were found in human leukemic cells of both granulocytic and erythroid lineages. G alpha16 proteins were revealed in myeloid cells as two bands (43 and 46 kD), implying that G alpha16 exist in short and long forms. The 43-kD form was predominant in normal granulomonocytic cells, whereas erythroid progenitors and platelets expressed mostly the 46-kD form. Both forms of G alpha16 proteins varied during cell differentiation: in normal hematopoietic cells, G alpha16 protein expression was high in CD34+ cells, then decreased sharply during granulocytic and erythroid differentiation. In leukemic granulocytic HL60 and NB4 cells, downregulation of G alpha16 proteins was an early event (8 hours) in the process of neutrophil differentiation; in contrast, expression of G alpha16 proteins remained high during normal monocytic differentiation and in HL60 cells differentiating into monocytes with phorbol myristate acetate (PMA) or gamma-interferon (IFNgamma). Finally, we found that primary myeloid leukemia blasts, as well as leukemic cell lines, expressed G alpha16 proteins at levels higher than those found in normal CD34+ progenitors. These observations suggest that it would be worthwhile to investigate a possible role for G alpha12 and G alpha16 proteins in the regulation of human myelopoiesis.