Signal-regulatory proteins (SIRP) are glycosylated, Ig-like cell surface receptors expressed on myeloid and neural cells. CDaSIRP proteins inhibit cell signaling by receptor tyrosine kinases and cytokine receptors by recruiting phosphatases to the membrane via inhibition motifs. Unlike CDa/SIRP, CD172b/SIRP lacks the ability to recruit SH2 domain-containing protein phosphatases. However, CD172b associates with the transmembrane protein DAP12/KARAP, and stimulation of this complex induces tyrosine phosphorylation, MAPK activation, and cellular activation. Therefore CD172a/SIRP and CD172b/SIRP may play complementary roles in signal regulation.