CD40 ligand binds to alpha 5beta 1 integrin and triggers cell signaling. Export

@article{citeulike:1010038, abstract = {It was originally thought that the critical role of the CD40 ligand (CD40L) in normal and inflammatory immune responses was mainly mediated through its interaction with the classical receptor, CD40. However, data from CD40L-/- and CD40-/- mice suggest that the CD40L-induced inflammatory immune response involves at least one other receptor. This hypothesis is supported by the fact CD40L stabilizes arterial thrombi through an alphaIIbbeta3-dependent mechanism. We provide evidence that soluble CD40L (sCD40L) binds to cells of the human monocytic U937 cell line in a CD40- and alphaIIbbeta3-independent manner. Binding of sCD40L to U937 cells was inhibited by anti-CD40L mAb 5C8, anti-alpha5beta1 mAb P1D6, and soluble alpha5beta1. The direct binding of sCD40L to purified alpha5beta1 was confirmed in a solid phase binding assay. Binding of sCD40L to alpha5beta1 was modulated by the form of alpha5beta1 expressed on the cell surface as the activation of alpha5beta1 by Mn(2)(+) or DTT resulted in the loss of sCD40L binding. Moreover, sCD40L induced the translocation of alpha5beta1 to the Triton X-100-insoluble fraction of U937 cells, the rapid activation of the MAPK pathways ERK1/2 and Il-8 gene expression. The binding of sCD40L to CD40 on BJAB cells, a alpha5beta1-negative B cell line, and the resulting activation of ERK1/2 was not inhibited by soluble alpha5beta1, suggesting that sCD40L can bind concomitantly to both receptors. These results document the existence of novel CD40L-dependent pathways of physiological relevance for cells expressing multiple receptors (CD40, alpha5beta1, and alphaIIbbeta3) for CD40L.}, address = {Centre de Recherche en immunologie et rhumatologie, CHUQ, Pavillon CHUL, universit\'{e} Laval, Qu\'{e}bec, Qu\'{e}bec G1V-4G2.}, author = {L\'{e}veill\'{e}, Claire and Bouillon, Marl\`{e}ne and Guo, Wen and Bolduc, Julie and Sharif-Askari, Ehssan and El-Fakhry, Youssef and Reyes-Moreno, Carlos and Lapointe, Rejean and Merhi, Yahye and Wilkins, John A A. and Mourad, Walid}, citeulike-article-id = {1010038}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M608342200}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/17182621}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=17182621}, day = {19}, doi = {10.1074/jbc.M608342200}, issn = {0021-9258}, journal = {J Biol Chem}, keywords = {a5b1, cd40l}, month = {December}, posted-at = {2006-12-22 23:06:56}, priority = {3}, title = {CD40 ligand binds to alpha 5beta 1 integrin and triggers cell signaling.}, url = {http://dx.doi.org/10.1074/jbc.M608342200}, year = {2006} }

TY - JOUR ID - citeulike:1010038 L3 - citeulike-article-id:1010038 N2 - It was originally thought that the critical role of the CD40 ligand (CD40L) in normal and inflammatory immune responses was mainly mediated through its interaction with the classical receptor, CD40. However, data from CD40L-/- and CD40-/- mice suggest that the CD40L-induced inflammatory immune response involves at least one other receptor. This hypothesis is supported by the fact CD40L stabilizes arterial thrombi through an alphaIIbbeta3-dependent mechanism. We provide evidence that soluble CD40L (sCD40L) binds to cells of the human monocytic U937 cell line in a CD40- and alphaIIbbeta3-independent manner. Binding of sCD40L to U937 cells was inhibited by anti-CD40L mAb 5C8, anti-alpha5beta1 mAb P1D6, and soluble alpha5beta1. The direct binding of sCD40L to purified alpha5beta1 was confirmed in a solid phase binding assay. Binding of sCD40L to alpha5beta1 was modulated by the form of alpha5beta1 expressed on the cell surface as the activation of alpha5beta1 by Mn(2)(+) or DTT resulted in the loss of sCD40L binding. Moreover, sCD40L induced the translocation of alpha5beta1 to the Triton X-100-insoluble fraction of U937 cells, the rapid activation of the MAPK pathways ERK1/2 and Il-8 gene expression. The binding of sCD40L to CD40 on BJAB cells, a alpha5beta1-negative B cell line, and the resulting activation of ERK1/2 was not inhibited by soluble alpha5beta1, suggesting that sCD40L can bind concomitantly to both receptors. These results document the existence of novel CD40L-dependent pathways of physiological relevance for cells expressing multiple receptors (CD40, alpha5beta1, and alphaIIbbeta3) for CD40L. JF - J Biol Chem SN - 0021-9258 AD - Centre de Recherche en immunologie et rhumatologie, CHUQ, Pavillon CHUL, université Laval, Québec, Québec G1V-4G2. TI - CD40 ligand binds to alpha 5beta 1 integrin and triggers cell signaling. KW - a5b1 KW - cd40l AU - Léveillé, Claire AU - Bouillon, Marlène AU - Guo, Wen AU - Bolduc, Julie AU - Sharif-Askari, Ehssan AU - El-Fakhry, Youssef AU - Reyes-Moreno, Carlos AU - Lapointe, Rejean AU - Merhi, Yahye AU - Wilkins, John A AU - Mourad, Walid PY - 2006/12/19/ UR - http://dx.doi.org/10.1074/jbc.M608342200 ER -