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First published online April 3, 2008
doi: 10.1242/10.1242/jcs.025163

Journal of Cell Science 121, 1235-1242 (2008)
Published by The Company of Biologists 2008
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Research Article

An alternatively spliced isoform of PECAM-1 is expressed at high levels in human and murine tissues, and suggests a novel role for the C-terminus of PECAM-1 in cytoprotective signaling

Carmen Bergom1,2,*, Cathy Paddock1,*, Cunji Gao1, Trudy Holyst1, Debra K. Newman1,3,4 and Peter J. Newman1,2,4,5,{ddagger}

1 Blood Research Institute, BloodCenter of Wisconsin, 8727 Watertown Plank Road, Milwaukee, WI 53201, USA
2 Department of Cell Biology, Medical College of Wisconsin, Milwaukee, WI, USA
3 Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI, USA
4 The Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI, USA
5 Department of Pharmacology, Medical College of Wisconsin, Milwaukee, WI, USA

{ddagger} Author for correspondence (e-mail: peter.newman{at}bcw.edu)

Accepted 21 January 2008

The Ig-ITIM family member PECAM-1 is expressed in vascular and endothelial cells, and its functions include suppression of mitochondria-dependent apoptosis. Previous studies have identified distinct PECAM-1 cytoplasmic domain splice variants at the mRNA, but not protein, level. Several relatively abundant mRNA isoforms lack exon 15 ({Delta}15) and would theoretically encode a protein with a truncated cytoplasmic domain and a unique C-terminal sequence. Using a novel rabbit polyclonal antibody that specifically recognizes {Delta}15 PECAM-1, we found that the {Delta}15 PECAM-1 isoform was expressed in human tissues, including brain, testes and ovary. This isoform was also expressed on the cell surface of human platelets, human umbilical vein endothelial cells (HUVECs) and the Jurkat T-cell leukemia, human erythroleukemia (HEL) and U937 histiocytic lymphoma cell lines. Furthermore, murine platelets and lung lysates demonstrated abundant amounts of exon-15-deficient PECAM-1. Functional studies revealed that {Delta}15 PECAM-1 retains both its homophilic binding capacity and its ability to signal by means of its immunoreceptor tyrosine-based inhibitory motif (ITIM) domains. {Delta}15 PECAM-1 was unable, however, to protect against apoptosis induced by overexpression of Bax or treatment with the chemotherapy agent etoposide. These studies suggest a novel role for the PECAM-1 C-terminus in cytoprotective signaling and highlight a need for further characterization of expression of PECAM-1 isoforms in normal and malignant tissues.

Key words: PECAM-1, CD31, Isoforms, Splice variants, Apoptosis


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