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Title

CD38 is associated with lipid rafts and upon receptor stimulation leads to Akt/protein kinase B and Erk activation in the absence of the CD3-ζ immune receptor tyrosine-based activation motifs

AuthorsZubiaur, Mercedes CSIC ORCID ; Fernández, Olga; Ferrero, E.; Salmerón, J.; Malissen, B.; Malavasi, F.; Sancho, Jaime CSIC ORCID
Issue Date2002
PublisherAmerican Society for Biochemistry and Molecular Biology
CitationJournal of Biological Chemistry 277: 13- 22 (2002)
AbstractT lymphocytes can be activated via the T cell receptor (TCR) or by triggering through a number of other cell surface structures, including the CD38 co-receptor molecule. Here, we show that in TCR+ T cells that express a CD3-ζ lacking the cytoplasmic domain, cross-linking with CD38- or CD3-specific monoclonal antibodies induces tyrosine phosphorylation of CD3-ε, ζ-associated protein-70, linker for activation of T cells, and Shc. Moreover, in these cells, anti-CD38 or anti-CD3 stimulation leads to protein kinase B/Akt and Erk activation, suggesting that the CD3-ζ-immunoreceptor tyrosine-based activation motifs are not required for CD38 signaling in T cells. Interestingly, in unstimulated T cells, lipid rafts are highly enriched in CD38, including the T cells lacking the cytoplasmic tail of CD3-ζ. Moreover, CD38 clustering by extensive cross-linking with an anti-CD38 monoclonal antibody and a secondary antibody leads to an increased resistance of CD38 to detergent solubilization, suggesting that CD38 is constitutively associated with membrane rafts. Consistent with this, cholesterol depletion with methyl-β-cyclodextrin substantially reduces CD38-mediated Akt activation while enhancing CD38-mediated Erk activation. CD38/raft association may improve the signaling capabilities of CD38 via formation of protein/lipid domains to which signaling-competent molecules, such as immunoreceptor tyrosine-based activation motif-bearing CD3 molecules and protein-tyrosine kinases, are recruited.
URIhttp://hdl.handle.net/10261/81820
DOIhttp://dx.doi.org/10.1074/jbc.M107474200
Identifiersdoi: 10.1074/jbc.M107474200
issn: 0021-9258
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