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Analysis of rodent platelet glycoprotein IIb: evidence for evolutionarily
conserved domains and alternative proteolytic processing
M Poncz and PJ Newman
Division of Hematology, Children's Hospital of Philadelphia, PA 19104.
Recently, the full-length primary amino acid sequence for human
glycoproteins (GP) IIb and IIIa have been derived from their respective
cDNAs. Potential functional domains within these proteins have been
proposed based primarily on homology with similar domains in other proteins
having known biologic function. To further understand the relationship
between structure and function of the platelet fibrinogen receptor, we have
begun comparative studies of the human GPIIb/IIIa receptor with the
corresponding rodent receptor. The rodent rGPIIb/IIIa receptor differs from
the human receptor, having low affinity for R.G.D- containing oligopeptides
and not binding at all to the C-terminus of the gamma chain of human
fibrinogen. We describe the structure of rodent platelet GPIIb derived from
a combination of peptide sequencing, and cDNA and partial genomic DNA
sequence analysis. The initial transcript is 1037 amino acid residues,
having 78% amino acid identity with its 1039 residue human analog. Both
heavy chains have the N- terminal sequence L.N.L.D, agreeing with the
consensus derived from other integrin family alpha heavy chains. All 18
cysteine residues occur at positions conserved in human GPIIb and the
vitronectin receptor alpha subunit VNR alpha. The putative calcium-binding
domains of the GPIIbs have a high level of amino acid identity (92%),
supporting the supposition that these regions have a critical biologic
role. The final 48 C-terminal amino acid residues of the heavy chain of
rodent GPIIb share only 56% identity with its human counterpart, and the
proposed cleavage site of human GPIIb into its heavy and light chains is
not present in the rodent sequence. Although we demonstrate that rodent
GPIIb is split into two subunits during its maturation, this process either
involves a different recognition sequence in the rodent or occurs at a
different site. Finally, partial genomic DNA sequence analysis indicates
that there are at least two rodent GPIIb genes: a normal gene, containing
introns in positions similar to those in the human gene, and a processed
pseudogene. The human haploid genome contains only a single GPIIb gene.
Volume 75,
Issue 6,
pp. 1282-1289,
03/15/1990
Copyright © 1990 by The American Society of Hematology
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