Tetraspanins regulate ADAM10-mediated cleavage of TNF-alpha and epidermal growth factor.
J Immunol
; 181(10): 7002-13, 2008 Nov 15.
Article
en En
| MEDLINE
| ID: mdl-18981120
Several cytokines and growth factors are released by proteolytic cleavage of a membrane-anchored precursor, through the action of ADAM (a disintegrin and metalloprotease) metalloproteases. The activity of these proteases is regulated through largely unknown mechanisms. In this study we show that Ab engagement of several tetraspanins (CD9, CD81, CD82) increases epidermal growth factor and/or TNF-alpha secretion through a mechanism dependent on ADAM10. The effect of anti-tetraspanin mAb on TNF-alpha release is rapid, not relayed by intercellular signaling, and depends on an intact MEK/Erk1/2 pathway. It is also associated with a concentration of ADAM10 in tetraspanin-containing patches. We also show that a large fraction of ADAM10 associates with several tetraspanins, indicating that ADAM10 is a component of the "tetraspanin web." These data show that tetraspanins regulate the activity of ADAM10 toward several substrates, and illustrate how membrane compartmentalization by tetraspanins can control the function of cell surface proteins such as ectoproteases.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Glicoproteínas de Membrana
/
Antígenos CD
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Factor de Necrosis Tumoral alfa
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Factor de Crecimiento Epidérmico
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Proteínas ADAM
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Proteína Kangai-1
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Secretasas de la Proteína Precursora del Amiloide
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Proteínas de la Membrana
Límite:
Humans
Idioma:
En
Revista:
J Immunol
Año:
2008
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Estados Unidos