Puromycin insensitive leucyl-specific aminopeptidase (PILSAP) is involved in the activation of endothelial integrins

✍ Scribed by Tetsuya Akada; Tohru Yamazaki; Hiroki Miyashita; Osamu Niizeki; Mayumi Abe; Akira Sato; Susumu Satomi; Yasufumi Sato

• Book ID: 102307980
• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 327 KB
• Volume: 193
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.10169

✦ Synopsis

Abstract

We previously reported that mouse orthologue of puromycin insensitive leucyl‐specific aminopeptidase (mPILSAP) played an important role in angiogenesis by regulating the proliferation and migration of endothelial cells (ECs) (Miyashita et al., 2002. Blood 99:3241–3249). Here, we examined the mechanism as to how mPILSAP regulates the migration of ECs. Cell adhesion through integrins plays a crucial role in cell migration, and ECs use at least type‐1 collagen receptor integrin α2β1, fibronectin receptor α5β1, and vitronectin receptors αvβ3 and αvβ5. mPILSAP antisense oligodeoxynucleotide (AS‐ODN) or leucinethiol (LT), a leucyl‐aminopeptidase inhibitor, did not affect the attachment but did significantly inhibit the spreading of cells of the murine endothelial cell line MSS31 when they were plated on vitronectin‐, fibronectin‐, or type‐1 collagen, although they did not affect the expression of integrin α2, α5, αv, β1, β3, and β5 subunits on the cell surface. AS‐ODN and LT also inhibited the tyrosine phosphorylation of FAK when cells were plated on vitronectin, fibronectin, or type‐1 collagen. This inhibition of cell spreading and of tyrosine phosphorylation of FAK could be negated by Mg^2+^. These results suggest that mPILSAP is involved in the activation of endothelial integrins. © 2002 Wiley‐Liss, Inc.