SPECIFIC EXPRESSION OF HETEROTRIMERIC G-PROTEINS G(12) AND G(16) DURING HUMAN MYELOID DIFFERENTIATION

To evaluate expression of heterotrimeric guanosine triphosphate (GTP)- binding proteins (G proteins) in human myeloid cells, we studied expre ssion at the protein level of their or subunits (G alpha, the subunits responsible for the name and specificity of G proteins) in normal hum an myeloid progenitors and mature blood cells. We found that G alpha(s ), Ga alpha(12), and G alpha(q/11) proteins were expressed at high lev els at all stages of granulomonocytic and erythroid differentiation, w hereas expression of Ga alpha(12) and G alpha(16) proteins in normal m yeloid cells was lineage-specific. G alpha(12) proteins were expressed in erythroid progenitors, monocytes, and platelets, but not in normal granulocytic cells. This lineage-specificity was lost in leukemic cel ls: G alpha(12) proteins were found in human leukemic cells of both gr anulocytic and erythroid lineages. G alpha(16) proteins were revealed in myeloid cells as two bands (43 and 46 kD), implying that G alpha(16 ) exist in short and long forms. The 43-kD form was predominant in nor mal granulomonocytic cells, whereas erythroid progenitors and platelet s expressed mostly the 46-kD form. Both forms of G alpha(16) proteins varied during cell differentiation: in normal hematopoietic cells, G a lpha(16) 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 alpha(16) protei ns was an early event (8 hours) in the process of neutrophil different iation; in contrast, expression of G alpha(16) proteins remained high during normal monocytic differentiation and in HL60 cells differentiat ing into monocytes with phor bol myristate acetate (PMA) or gamma-inte rferon (IFN gamma). Finally, we found that primary myeloid leukemia bl asts, as well as leukemic cell lines, expressed G alpha(16) proteins a t levels higher than those found in normal CD34(+) progenitors. These observations suggest that it would be worthwhile to investigate 8 poss ible role for G alpha(12) and G alpha(16) proteins in the regulation o f human myelopoiesis.