Journal
JOURNAL OF CELL SCIENCE
Volume 119, Issue 16, Pages 3424-3434Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.03067
Keywords
uPA; uPAR signaling; cytoskeleton
Categories
Funding
- NCI NIH HHS [CA-40758] Funding Source: Medline
Ask authors/readers for more resources
The serine protease urokinase (uPA) binds to the urokinase receptor (uPAR) through its growth-factor domain (GFD, residues 1-49), affecting cell migration, adhesion and growth. Here, we show that uPA can promote cytoskeletal rearrangements and directional cell migration in a GFD-independent manner, through a new and specific interaction between an internal uPA domain coined 'connecting peptide' (residues 132-158) and cell-surface integrin alpha v beta 5. Remarkably, a peptide corresponding to this region (CPp, residues 135-158) retains the ability to bind to alpha v beta 5, eliciting cytoskeletal rearrangements and directing cell migration at a concentration as low as 1-10 pM. These effects are lost in cells not expressing uPAR, indicating that the uPAR is required for CPp-dependent signaling. Furthermore, the CPp-alpha v beta 5-integrin interaction enhances F-actin-enriched protrusions and cell migration induced by the well-established interaction between the uPAR-binding peptide (GFDp, residues 12-32) of uPA and uPAR. These results provide new insight into the function of uPA, which - through individual domains - can engage two different surface receptors (uPAR and alpha v beta 5 integrin), thus initiating and potentiating intracellular signaling and migration.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available