NDLI: CD2AP/SHIP1 complex positively regulates plasmacytoid dendritic cell receptor signaling by inhibiting the E3 ubiquitin ligase Cbl.

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CD2AP/SHIP1 complex positively regulates plasmacytoid dendritic cell receptor signaling by inhibiting the E3 ubiquitin ligase Cbl.

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CD2AP/SHIP1 complex positively regulates plasmacytoid dendritic cell receptor signaling by inhibiting the E3 ubiquitin ligase Cbl.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Chaperot, Laurence Du, Qiumei Bover, Laura Cao, Wei Qin, Jun Sun, Shao-Cong Liu, Yong-Jun Plumas, Joel Bao, Musheng Hanabuchi, Shino Facchinetti, Valeria
Description	Country affiliation: United States Author Affiliation: Bao M ( Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.)
Abstract	The human plasmacytoid dendritic cell (pDC) receptor BDCA2 forms a complex with the adaptor FcÎµR1Î³ to activate an ITAM-signaling cascade. BDCA2 receptor signaling negatively regulates the TLR7/9-mediated type 1 IFN responses in pDCs, which may play a key role in controlling self-DNA/RNA-induced autoimmunity. We report in this article that CD2-associated adaptor protein (CD2AP), which is highly expressed in human pDCs, positively regulates BDCA2/FcÎµR1Î³ receptor signaling. By immunoprecipitation and mass spectrometry analyses, we found that CD2AP bound to SHIP1. Knockdown of CD2AP or SHIP1 reduced the BDCA2/FcÎµR1Î³-mediated ITAM signaling and blocked its inhibition of TLR9-mediated type 1 IFN production. Knockdown of CD2AP or SHIP1 also enhanced the ubiquitination and degradation of Syk and FcÎµR1Î³ that was mediated by the E3 ubiquitin ligase Cbl. This led us to discover that, upon BDCA2 cross-linking, the CD2AP/SHIP1 complex associated with Cbl and inhibited its E3 ubiquitin ligase activity. In human primary pDCs, cross-linking of the BDCA2/FcÎµR1Î³ complex induced the recruitment of the CD2AP/SHIP1/Cbl complex to the plasma membrane of pDCs, where it colocalized with the BDCA2/FcÎµR1Î³ complex. Therefore, CD2AP positively regulates BDCA2/FcÎµR1Î³ signaling by forming a complex with SHIP1 to inhibit the E3 ubiquitin ligase Cbl.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1200887
Journal	The Journal of Immunology
Issue Number	2
Volume Number	189
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-07-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Adaptor Proteins, Signal Transducing Physiology Cytoskeletal Proteins Dendritic Cells Immunology Multiprotein Complexes Phosphoric Monoester Hydrolases Proto-oncogene Proteins C-cbl Antagonists & Inhibitors Metabolism Signal Transduction Up-regulation Cells, Cultured Cross-linking Reagents Enzymology Hek293 Cells Lectins, C-type Membrane Glycoproteins Receptors, Immunologic Research Support, N.i.h., Extramural Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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