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The Journal of Immunology, 2000, 164: 9-12.
Copyright © 2000 by The American Association of Immunologists

CUTTING EDGE

Cutting Edge: Signal-Regulatory Protein ß1 Is a DAP12-Associated Activating Receptor Expressed in Myeloid Cells1

Jes Dietrich2,*, Marina Cella*, Martina Seiffert{dagger}, Hans-Jörg Bühring{dagger} and Marco Colonna2,*

* Basel Institute for Immunology, Basel, Switzerland; and {dagger} University of Tübingen, Department of Internal Medicine II, Division of Hematology, Immunology and Oncology, Tübingen, Germany

Signal-regulatory proteins (SIRPs) are cell-surface glycoproteins expressed on myeloid and neural cells that have been shown to recruit SH2 domain-containing protein phosphatase 1 (SHP-1) and SHP-2 and to regulate receptor tyrosine kinase-coupled signaling. One SIRP of unknown function, designated SIRPß1, contains a short cytoplasmic domain that lacks sequence motifs capable of recruiting SHP-1 and SHP-2. Using a SIRP-specific mAb, we show that SIRPß1 is expressed in monocytes and dendritic cells and associates with the signal transduction molecule DAP12. SIRPß1/DAP12 complex formation was required for efficient cell-surface expression of SIRPß1. Stimulation of this complex induced tyrosine phosphorylation, mitogen-activated protein kinase activation, and cellular activation. Thus, SIRPß1 is a new DAP12-associated receptor involved in the activation of myeloid cells.




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