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Interaction of CD154 with different receptors and its role in bidirectional signals.
Alturaihi, Haydar; Hassan, Ghada S; Al-Zoobi, Loubna; Salti, Suzanne; Darif, Youssef; Yacoub, Daniel; El Akoum, Souhad; Oudghiri, Mounia; Merhi, Yahye; Mourad, Walid.
Afiliação
  • Alturaihi H; Laboratoire d'immunologie cellulaire et moléculaire, Centre de Recherche-Centre Hospitalier de l'Université de Montréal (CR-CHUM), Montréal, Canada.
Eur J Immunol ; 45(2): 592-602, 2015 Feb.
Article em En | MEDLINE | ID: mdl-25403978
In addition to its classical receptor, CD40, it is now well established that CD154 also binds αIIbß3, α5ß1, and αMß2 integrins. Although these integrins are all members of the same family, they bind CD154 differently. The current investigation aims to analyze the interaction of CD154 with α5ß1 and αMß2 and investigate its role in bidirectional signals in various human cell lines. Results obtained herein indicate that the CD154 residues involved in the interaction with α5ß1 are N151 and Q166, whereas those involved in αMß2 binding are common to residues required for CD40, namely Y145 and R203. Soluble CD40/CD154 or αMß2/CD154 complexes do not interfere with the binding of CD154 to α5ß1-positive cells, but inhibit the binding of CD154 to CD40- or αMß2-positive cells, respectively. Ligation of CD154 on CD154-positive cells with soluble CD40, αIIbß3, α5ß1, or αMß2 stimulates intracellular signaling, including MAPK phosphorylation. Given that CD154 exists as a trimer, our data strongly suggest that CD154 may bind concomitantly to two receptors of the same or different family, and biologically activate cells expressing both receptors. The characterization of CD154/receptor interactions helps the identification of new therapeutic targets for the prevention and/or treatment of CD154-associated autoimmune and inflammatory diseases.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Antígeno de Macrófago 1 / Antígenos CD40 / Ligante de CD40 / Integrina alfa5beta1 Idioma: En Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Antígeno de Macrófago 1 / Antígenos CD40 / Ligante de CD40 / Integrina alfa5beta1 Idioma: En Ano de publicação: 2015 Tipo de documento: Article