First published online April 3, 2008
Journal of Cell Science 121, 802e (2008)
© The Company of Biologists Limited
The changing face of PECAM-1
In addition to its roles in adhesion and migration, the cell-surface protein PECAM-1 also functions to protect cells against mitochondrion-dependent apoptosis. Several alternatively spliced mRNAs that have the potential to encode variant PECAM-1 isoforms have been identified, but the presence of these isoforms has not been convincingly demonstrated at the protein level. Peter J. Newman and colleagues (p. 1235) now demonstrate the expression of
15 PECAM-1, an isoform that is encoded by PECAM1 mRNA that lacks exon 15. Using a novel antibody that is specific for the variant C-terminus of
15 PECAM-1, the authors show that this isoform is expressed in several human and mouse tissues. In addition,
15 PECAM-1 localises to cell-cell borders, just as the full-length protein does. The isoform is tyrosine phosphorylated in response to vanadate, and the phosphorylated form co-immunoprecipitates with the phosphatase SHP-2, indicating that it can initiate signalling cascades in a similar manner to full-length PECAM-1. However, unlike the full-length protein,
15 PECAM-1 does not protect HEK293 cells from apoptosis that is induced by the overexpression of Bax or by etoposide treatment. The authors propose, therefore, that the C-terminus of PECAM-1 has a novel role in cytoprotection.
Related articles in JCS:
- 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 Bergom, Cathy Paddock, Cunji Gao, Trudy Holyst, Debra K. Newman, and Peter J. Newman
JCS 2008 121: 1235-1242.
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