The earliest marker of the megakaryocyte lineage in human bone marrow is a heterodimeric complex of
glycoproteins IIb (GPIIb) and IIIa (
GPIIIa). GPIIb-IIIa is a member of the
integrin family and serves as a receptor for
fibrinogen and other adhesive
glycoproteins on the surface of activated blood platelets. Mature platelet GPIIb is processed from a single precursor
peptide into a
disulfide-linked GPIIb alpha and GPIIb beta chain. To study possible mechanisms which could determine
ligand specificity of the GPIIb-IIIa complex we investigated whether there are multiple forms of GPIIb
mRNA by screening an unamplified lambda gt10 human
erythroleukemia cell cDNA library. Four GPIIb clones were isolated and sequenced. Two contained a 102-nucleotide in-frame deletion corresponding to 34
amino acids in the extracellular domain of GPIIb beta. Polymerase chain reaction amplification of human
erythroleukemia cell
cDNA confirmed the presence of two different transcripts. Normal genomic DNA sequence was shown to contain consensus splice-donor and
splice-acceptor sites indicating a 102-base pair exon that is spliced in or out. Using primers specific for either transcript, both forms of GPIIb
mRNA were identified by the polymerase chain reaction in normal human platelets and megakaryocytes, but not in reticulocytes or two white blood cell lines. These data provide evidence for two forms of GPIIb in platelets and megakaryocytes and suggest a mechanism for variations in receptor
ligand affinity or localization.