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.
Urokinase receptor activation by a novel interaction between connecting peptide region of Urokinase and αvβ5 Integrin Journal of Cell Science, 119, 3424-3434, 2006 / Franco, P; Vocca, I; Carriero, M. V; Alfano, D; Cito, L; Longanesi, Cattani; I, ; Grieco, Paolo; P, Ossowski; L, Stoppelli; M., P.. - In: JOURNAL OF CELL SCIENCE. - ISSN 0021-9533. - STAMPA. - 119:(2006), pp. 3424-3434. [10.1242/jcs.03067]
Urokinase receptor activation by a novel interaction between connecting peptide region of Urokinase and αvβ5 Integrin Journal of Cell Science, 119, 3424-3434, 2006
GRIECO, PAOLO;
2006
Abstract
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.File | Dimensione | Formato | |
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