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The Journal of Immunology, 2003, 171: 1901-1908.
Copyright © 2003 by The American Association of Immunologists

The CD43 Coreceptor Molecule Recruits the {zeta}-Chain as Part of Its Signaling Pathway1

Mario Ernesto Cruz-Muñoz*, Enrique Salas-Vidal*, Norma Salaiza-Suazo{dagger}, Ingeborg Becker{dagger}, Gustavo Pedraza-Alva2,* and Yvonne Rosenstein3,*

* Instituto de Biotecnología and {dagger} Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico

CD43 is an abundant cell surface sialoglycoprotein implicated in hemopoietic cell adhesion and activation. Cell stimulation through CD43 results in recruitment of different signaling proteins, including members of the Src family kinases, Syk, phospholipase C{gamma}2, the adapter protein Shc, the guanine nucleotide exchange factor Vav, and activation of protein kinase C. In this study, we report that in human T lymphocytes, the {zeta}-chain is part of the CD43 signaling pathway. Upon CD43 engagement, the {zeta}-chain was tyrosine-phosphorylated, generating docking sites for tyrosine-phosphorylated {zeta}-associated protein of 70 kDa and Vav. In vitro kinase assays suggested that {zeta}-associated protein of 70 kDa could account for the kinase activity associated with the {zeta}-chain following CD43 engagement. Cross-linking CD43 on the surface of the Lck-deficient JCaM.1 cells failed to phosphorylate the {zeta}-chain and associated proteins, suggesting that Lck is a key element in the CD43 signaling pathway leading to {zeta} phosphorylation. CD43 engagement with beads coated with anti-CD43 mAb resulted in concentration of the {zeta}-chain toward the bead attachment site, but interestingly, the distribution of the T cell Ag receptor complex remained unaffected. Recruitment of the {zeta}-chain through CD43-mediated signals was not restricted to T lymphocytes because phosphorylation and redistribution of the {zeta}-chain was also observed in NK cells. Our results provide evidence that the {zeta}-chain functions as a scaffold molecule in the CD43 signaling pathway, favoring the recruitment and formation of downstream signaling complexes involved in the CD43-mediated cell activation of T lymphocytes and other leukocytes such as NK cells.




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