Biological activity of soluble CD100. I. The extracellular region of CD100 is released from the surface of T lymphocytes by regulated proteolysis.
J Immunol
; 166(7): 4341-7, 2001 Apr 01.
Article
en En
| MEDLINE
| ID: mdl-11254687
CD100 is the first semaphorin described in lymphoid tissues, where it has been shown to be associated with a serine kinase activity. Semaphorins are molecules involved in axon pathfinding during nerve development and act as repellent guidance cues. In the nervous system semaphorins exist as either membrane-bound or secreted forms. We report here a spontaneous processing of membrane CD100, suggesting that it is also produced as a diffusable semaphorin from lymphoid cells. Monomeric and homodimeric forms of CD100 are expressed by T lymphocytes and CD100-transfected fibroblasts. We demonstrate that CD100 is released through a proteolytic process blocked by metalloprotease inhibitors. In T cells, only soluble CD100 dimers are produced, suggesting that CD100 dimerization is required for proteolysis. In agreement, we observe that increasing membrane dimers strongly favors shedding of the molecule. By expressing a CD100 molecule mutated at cysteine 674 into a COS cell system, we additionally demonstrate that this particular residue in the extracellular domain of the molecule is required for dimerization. Finally, we show that staurosporine, a serine kinase inhibitor, enhances the membrane cleavage of CD100. Together these results demonstrate that membrane CD100 is cleaved by a metalloprotease-dependent process, which is probably regulated by phosphorylation. Mainly, these findings shed light on a possible function for the semaphorin region of CD100 as a long range guidance cue in the immune system.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Endopeptidasas
/
Glicoproteínas de Membrana
/
Linfocitos T
/
Antígenos CD
/
Semaforinas
/
Espacio Extracelular
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Immunol
Año:
2001
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Estados Unidos