S. Tenailleau et al., SPECIFIC EXPRESSION OF HETEROTRIMERIC G-PROTEINS G(12) AND G(16) DURING HUMAN MYELOID DIFFERENTIATION, Experimental hematology, 25(9), 1997, pp. 927-934
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.