Cutting edge: Signal-regulatory protein beta 1 is a DAP12-associated activating receptor expressed in myeloid cells

Signal-regulatory proteins (SIRPs) are cell-surface glycoproteins expressed on myeloid and neural cells that have been shown to recruit SH2 domain-con taining protein phosphatase 1 (SHP-1) and SHP-2 and to regulate receptor ty rosine kinase-coupled signaling. One SIRP of unknown function, designated S IRP beta 1, contains a short cytoplasmic domain that lacks sequence motifs capable of recruiting SHP-1 and SHP-2, Using a SIRP-specific mAb, we show t hat SIRP beta 1 is expressed in monocytes and dendritic cells and associate s with the signal transduction molecule DAP12. SIRP beta 1/DAP12 complex fo rmation was required for efficient cell-surface expression of SIRP beta 1, Stimulation of this complex induced tyrosine phosphorylation, mitogen-activ ated protein kinase activation, and cellular activation. Thus, SIRP beta 1 is a new DAP12-associated receptor involved in the activation of myeloid ce lls.