The platelet glycoprotein Ib-V-IX system: regulation of gene expression.
Platelet glycoproteins (GPs) Ib-V-IX form the surface receptor for von Willebrand factor, and this receptor-ligand interaction mediates the shear-dependent adhesion of platelets to damaged arterial vessel walls. The receptor is a multicomponent structure consisting of four distinct polypeptides (heterodimeric GPIb: Ib alpha-Mr143k and Ib beta-Mr22k; GPV-Mr83k; GPIX-Mr20k), and each of the four cDNAs and genes has been cloned and characterized. The genes appear to have evolved from a common progenitor genomic sequence related to that encoding GPIX. They share simple structures with few introns and possess common consensus regulatory sequences (GATA, ets, Sp-1) in their 5' flanks. Both the GPIb alpha and the GPIX promoters have been analyzed by transfection of reporter constructs into hematopoietic and nonhematopoietic cells. The promoters function in a tissue-specific fashion, and gel shift and mutational analyses indicate that GATA and ets sequences regulate activity. In the case of the GPIX promoter, footprints confirm the role of the ets-related consensus region. Recent studies of GPIb beta transcriptional regulation suggest that an aberrant polyadenylation signal, located in the 3' end of the gene immediately upstream of the GPIb beta gene, allows in vitro expression of a rare extended fusion transcript encoding both the upstream protein and GPIb beta. Little detailed information is available in regard to expression of the GPV gene. In summary, the genes of the GPIb-V-IX system display features of other megakaryocyte/platelet genes, but the unique regulatory events that direct the selective expression of these genes in megakaryocytes remain to be defined.
Roth
G J
GJ
Hematology Section, Medical and Research Services, Seattle Veterans Administration Medical Center and the University of Washington, 98108, USA.
Yagi
M
M
Bastian
L S
LS
D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D007438:Introns; D008954:Models, Biological; D010974:Platelet Aggregation / Q000235:genetics*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011061:Poly A / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014018:Tissue Distribution; D014158:Transcription, Genetic; D014162:Transfection
D018076:DNA, Complementary; D019038:Platelet Glycoprotein GPIb-IX Complex; D011993:Recombinant Fusion Proteins; D011061:Poly A