Adapter proteins SLP-76 and BLNK both are expressed by murine macrophages and are linked to signaling via Fc gamma receptors I and II/III

The SLP-76 (Src homology 2 domain-containing leukocyte protein of 76 kDa) a dapter protein is expressed in T cells and myeloid cells, whereas its homol ogue BLNK (B cell linker protein) is expressed in B cells. SLP-76 and BLNK link immunoreceptor tyrosine-based activation motif-containing receptors to signaling molecules that include phospholipase C-gamma, mitogen-activated protein kinases, and the GTPases Ras and Rho, SLP-76 plays a critical role in T cell receptor, Fc epsilon RI and gpVI collagen receptor signaling, and participates in signaling via Fc gamma R and killer cell inhibitory recept ors, BLNK plays a critical role in B cell receptor signaling. We show that murine bone marrow-derived macrophages express both SLP-76 and BLNK, Select ive ligation of Fc gamma RI and Fc gamma RII/III resulted in tyrosine phosp horylation of both SLP-76 and BLNK, SLP-76(-/-) bone marrow-derived macroph ages display Fc gamma R-mediated tyrosine phosphorylation of Syk, phospholi pase C-gamma 2, and extracellular signal regulated kinases 1 and 2, and nor mal Fc gamma R-dependent phagocytosis. These data suggest that both SLP-76 and BLNK are coupled to Fc gamma R signaling in murine macrophages.