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Organization of the gene for human platelet/endothelial cell adhesion
molecule-1 shows alternatively spliced isoforms and a functionally complex
cytoplasmic domain
NE Kirschbaum, RJ Gumina and PJ Newman
Blood Research Institute, Blood Center of Southeastern Wisconsin, Milwaukee
53233.
Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a cell-cell
adhesion molecule that is expressed on circulating platelets, on
leukocytes, and at the intercellular junctions of vascular endothelial
cells and mediates the interactions of these cells during the process of
transendothelial cell migration. The cDNA for PECAM-1 encodes an open
reading frame of 738 amino acids (aa) that is organized into a 27- aa
signal peptide, a 574-aa extracellular domain composed of 6 Ig homology
units, and a relatively long cytoplasmic tail of 118 aa containing multiple
sites for posttranslational modification and postreceptor signal
transduction. To provide a molecular basis for the precise evaluation of
the structure and function of this transmembrane glycoprotein, we have
determined the organization of the human PECAM-1 gene. The PECAM-1 gene,
which has been localized to human chromosome 17, is a single-copy gene of
approximately 65 kb in length and is broken into 16 exons by introns
ranging in size from 86 to greater than 12,000 bp in length. Typical of
other members of the Ig superfamily, each of the extracellular Ig homology
domains is encoded by a separate exon, consistent with PECAM-1 having
arisen by gene duplication and exon shuffling of ancestral Ig superfamily
genes. However, the cytoplasmic domain was found to be surprisingly
complex, being encoded by seven short exons that may represent discrete
functional entities. Alternative splicing of the cytoplasmic tail appears
to generate multiple PECAM-1 isoforms that may regulate phosphorylation,
cytoskeletal association, and affinity modulation of the mature protein.
Finally, a processed pseudogene having 76% identity with PECAM- 1 cDNA was
identified and localized to human chromosome 3. These findings should have
important implications for structure/function analysis of PECAM-1 and its
role in vascular adhesive interactions.
Volume 84,
Issue 12,
pp. 4028-4037,
12/15/1994
Copyright © 1994 by The American Society of Hematology
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