G-ALPHA-16, A G-PROTEIN ALPHA SUBUNIT SPECIFICALLY EXPRESSED IN HEMATOPOIETIC-CELLS

Signal-transduction pathways mediated by guanine nucleotide-binding regulatory proteins (G proteins) determine many of the responses of hematopoietic cells. A recently identified gene encoding a G protein alpha-subunit, G-alpha-16, is specifically expressed in human cells of the hematopoietic lineage. The G-alpha-16 cDNA encodes a protein with predicted M(r) of 43,500, which resembles the G(q) class of alpha-subunits and does not include a pertussis toxin ADP-ribosylation site. In comparison with other G protein alpha-subunits, the G-alpha-16 predicted protein has distinctive amino acid sequences in the amino terminus, the region A guanine nucleotide-binding domain, and in the carboxyl-terminal third of the protein. Cell lines of myelomonocytic and T-cell phenotype express the G-alpha-16 gene, but no expression is detectable in two B-cell lines or in nonhematopoietic cell lines. G-alpha-16 gene expression is down-regulated in HL-60 cells induced to differentiate to neutrophils with dimethyl sulfoxide. Antisera generated from synthetic peptides that correspond to two regions of G-alpha-16 specifically react with a protein of 42- to 43-kDa in bacterial strains that overexpress G-alpha-16 and in HL-60 membranes. This protein is decreased in membranes from dimethyl sulfoxide-differentiated HL-60 cells and is not detectable in COS cell membranes. The restricted expression of this gene suggests that G-alpha-16 regulates cell-type-specific signal-transduction pathways, which are not inhibited by pertussis toxin.