2024-03-29T14:58:40Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/749702018-05-04T09:08:48Zcom_10261_79com_10261_1col_10261_332
2013-04-23T17:17:18Z
urn:hdl:10261/74970
The sheddase activity of ADAM17/TACE is regulated by the tetraspanin CD9
Gutiérrez-López, María Dolores
Gilsanz, Álvaro
Yáñez-Mó, María
Ovalle, Susana
Lafuente, Esther M.
Domínguez, Carmen
Monk, Peter N.
González-Álvaro, Isidoro
Sánchez-Madrid, Francisco
Cabañas, Carlos
Ministerio de Ciencia e Innovación (España)
Fundación Mutua Madrileña
Instituto de Salud Carlos III
Consejo Superior de Investigaciones Científicas (España)
ADAM17
Tetraspanins
CD9
TACE
TNF-a
ICAM-1
ADAM17/TACE is a metalloproteinase
responsible for the shedding of the proinflammatory cytokine TNF-a and many other cell surface proteins involved in
development, cell adhesion, migration, differentiation, and
proliferation. Despite the important biological function of
ADAM17, the mechanisms of regulation of its metalloproteinase activity remain largely unknown. We report here that
the tetraspanin CD9 and ADAM17 partially co-localize on
the surface of endothelial and monocytic cells. In situ
proximity ligation, co-immunoprecipitation, crosslinking,
and pull-down experiments collectively demonstrate a direct
association between these molecules. Functional studies
reveal that treatment with CD9-specific antibodies or
neoexpression of CD9 exert negative regulatory effects on
ADAM17 sheddase activity. Conversely, CD9 silencing
increased the activity of ADAM17 against its substrates
TNF-a and ICAM-1. Taken together, our results show that
CD9 associates with ADAM17 and, through this interaction,
negatively regulates the sheddase activity of ADAM17
2013-04-23T17:17:18Z
2013-04-23T17:17:18Z
2011
artículo
Cellular and Molecular Life Sciences 68(19): 3275-3292
1420-682X
http://hdl.handle.net/10261/74970
10.1007/s00018-011-0639-0
http://dx.doi.org/10.13039/501100004837
http://dx.doi.org/10.13039/100008061
http://dx.doi.org/10.13039/501100004587
http://dx.doi.org/10.13039/501100003339
eng
http://dx.doi.org/10.1007/s00018-011-0639-0
closedAccess
Springer