Fibulin-5 binds urokinase-type plasminogen activator and mediates urokinase-stimulated β1-integrin-dependent cell migration.
uPA (urokinase-type plasminogen activator) stimulates cell migration through multiple pathways, including formation of plasmin and extracellular metalloproteinases, and binding to the uPAR (uPA receptor; also known as CD87), integrins and LRP1 (low-density lipoprotein receptor-related protein 1) whi...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2012
|
| _version_ | 1826262031594946560 |
|---|---|
| author | Kapustin, A Stepanova, V Aniol, N Cines, D Poliakov, A Yarovoi, S Lebedeva, T Wait, R Ryzhakov, G Parfyonova, Y Gursky, Y Yanagisawa, H Minashkin, M Beabealashvilli, R Vorotnikov, A Bobik, A Tkachuk, V |
| author_facet | Kapustin, A Stepanova, V Aniol, N Cines, D Poliakov, A Yarovoi, S Lebedeva, T Wait, R Ryzhakov, G Parfyonova, Y Gursky, Y Yanagisawa, H Minashkin, M Beabealashvilli, R Vorotnikov, A Bobik, A Tkachuk, V |
| author_sort | Kapustin, A |
| collection | OXFORD |
| description | uPA (urokinase-type plasminogen activator) stimulates cell migration through multiple pathways, including formation of plasmin and extracellular metalloproteinases, and binding to the uPAR (uPA receptor; also known as CD87), integrins and LRP1 (low-density lipoprotein receptor-related protein 1) which activate intracellular signalling pathways. In the present paper we report that uPA-mediated cell migration requires an interaction with fibulin-5. uPA stimulates migration of wild-type MEFs (mouse embryonic fibroblasts) (Fbln5+/+ MEFs), but has no effect on fibulin-5-deficient (Fbln5-/-) MEFs. Migration of MEFs in response to uPA requires an interaction of fibulin-5 with integrins, as MEFs expressing a mutant fibulin-5 incapable of binding integrins (Fbln(RGE/RGE) MEFs) do not migrate in response to uPA. Moreover, a blocking anti-(human β1-integrin) antibody inhibited the migration of PASMCs (pulmonary arterial smooth muscle cells) in response to uPA. Binding of uPA to fibulin-5 generates plasmin, which excises the integrin-binding N-terminal cbEGF (Ca2+-binding epidermal growth factor)-like domain, leading to loss of β1-integrin binding. We suggest that uPA promotes cell migration by binding to fibulin-5, initiating its cleavage by plasmin, which leads to its dissociation from β1-integrin and thereby unblocks the capacity of integrin to facilitate cell motility. |
| first_indexed | 2024-03-06T19:29:56Z |
| format | Journal article |
| id | oxford-uuid:1d1c3335-2b5c-4c5c-a02e-4d61ebdf4395 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:29:56Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:1d1c3335-2b5c-4c5c-a02e-4d61ebdf43952022-03-26T11:09:08ZFibulin-5 binds urokinase-type plasminogen activator and mediates urokinase-stimulated β1-integrin-dependent cell migration.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1d1c3335-2b5c-4c5c-a02e-4d61ebdf4395EnglishSymplectic Elements at Oxford2012Kapustin, AStepanova, VAniol, NCines, DPoliakov, AYarovoi, SLebedeva, TWait, RRyzhakov, GParfyonova, YGursky, YYanagisawa, HMinashkin, MBeabealashvilli, RVorotnikov, ABobik, ATkachuk, VuPA (urokinase-type plasminogen activator) stimulates cell migration through multiple pathways, including formation of plasmin and extracellular metalloproteinases, and binding to the uPAR (uPA receptor; also known as CD87), integrins and LRP1 (low-density lipoprotein receptor-related protein 1) which activate intracellular signalling pathways. In the present paper we report that uPA-mediated cell migration requires an interaction with fibulin-5. uPA stimulates migration of wild-type MEFs (mouse embryonic fibroblasts) (Fbln5+/+ MEFs), but has no effect on fibulin-5-deficient (Fbln5-/-) MEFs. Migration of MEFs in response to uPA requires an interaction of fibulin-5 with integrins, as MEFs expressing a mutant fibulin-5 incapable of binding integrins (Fbln(RGE/RGE) MEFs) do not migrate in response to uPA. Moreover, a blocking anti-(human β1-integrin) antibody inhibited the migration of PASMCs (pulmonary arterial smooth muscle cells) in response to uPA. Binding of uPA to fibulin-5 generates plasmin, which excises the integrin-binding N-terminal cbEGF (Ca2+-binding epidermal growth factor)-like domain, leading to loss of β1-integrin binding. We suggest that uPA promotes cell migration by binding to fibulin-5, initiating its cleavage by plasmin, which leads to its dissociation from β1-integrin and thereby unblocks the capacity of integrin to facilitate cell motility. |
| spellingShingle | Kapustin, A Stepanova, V Aniol, N Cines, D Poliakov, A Yarovoi, S Lebedeva, T Wait, R Ryzhakov, G Parfyonova, Y Gursky, Y Yanagisawa, H Minashkin, M Beabealashvilli, R Vorotnikov, A Bobik, A Tkachuk, V Fibulin-5 binds urokinase-type plasminogen activator and mediates urokinase-stimulated β1-integrin-dependent cell migration. |
| title | Fibulin-5 binds urokinase-type plasminogen activator and mediates urokinase-stimulated β1-integrin-dependent cell migration. |
| title_full | Fibulin-5 binds urokinase-type plasminogen activator and mediates urokinase-stimulated β1-integrin-dependent cell migration. |
| title_fullStr | Fibulin-5 binds urokinase-type plasminogen activator and mediates urokinase-stimulated β1-integrin-dependent cell migration. |
| title_full_unstemmed | Fibulin-5 binds urokinase-type plasminogen activator and mediates urokinase-stimulated β1-integrin-dependent cell migration. |
| title_short | Fibulin-5 binds urokinase-type plasminogen activator and mediates urokinase-stimulated β1-integrin-dependent cell migration. |
| title_sort | fibulin 5 binds urokinase type plasminogen activator and mediates urokinase stimulated β1 integrin dependent cell migration |
| work_keys_str_mv | AT kapustina fibulin5bindsurokinasetypeplasminogenactivatorandmediatesurokinasestimulatedb1integrindependentcellmigration AT stepanovav fibulin5bindsurokinasetypeplasminogenactivatorandmediatesurokinasestimulatedb1integrindependentcellmigration AT anioln fibulin5bindsurokinasetypeplasminogenactivatorandmediatesurokinasestimulatedb1integrindependentcellmigration AT cinesd fibulin5bindsurokinasetypeplasminogenactivatorandmediatesurokinasestimulatedb1integrindependentcellmigration AT poliakova fibulin5bindsurokinasetypeplasminogenactivatorandmediatesurokinasestimulatedb1integrindependentcellmigration AT yarovois fibulin5bindsurokinasetypeplasminogenactivatorandmediatesurokinasestimulatedb1integrindependentcellmigration AT lebedevat fibulin5bindsurokinasetypeplasminogenactivatorandmediatesurokinasestimulatedb1integrindependentcellmigration AT waitr fibulin5bindsurokinasetypeplasminogenactivatorandmediatesurokinasestimulatedb1integrindependentcellmigration AT ryzhakovg fibulin5bindsurokinasetypeplasminogenactivatorandmediatesurokinasestimulatedb1integrindependentcellmigration AT parfyonovay fibulin5bindsurokinasetypeplasminogenactivatorandmediatesurokinasestimulatedb1integrindependentcellmigration AT gurskyy fibulin5bindsurokinasetypeplasminogenactivatorandmediatesurokinasestimulatedb1integrindependentcellmigration AT yanagisawah fibulin5bindsurokinasetypeplasminogenactivatorandmediatesurokinasestimulatedb1integrindependentcellmigration AT minashkinm fibulin5bindsurokinasetypeplasminogenactivatorandmediatesurokinasestimulatedb1integrindependentcellmigration AT beabealashvillir fibulin5bindsurokinasetypeplasminogenactivatorandmediatesurokinasestimulatedb1integrindependentcellmigration AT vorotnikova fibulin5bindsurokinasetypeplasminogenactivatorandmediatesurokinasestimulatedb1integrindependentcellmigration AT bobika fibulin5bindsurokinasetypeplasminogenactivatorandmediatesurokinasestimulatedb1integrindependentcellmigration AT tkachukv fibulin5bindsurokinasetypeplasminogenactivatorandmediatesurokinasestimulatedb1integrindependentcellmigration |