title: Adapter proteins SLP-76 and BLNK both are expressed by murine macrophages and are linked to signaling via Fcgamma receptors I and II/III.
abstract: The SLP-76 (Src homology 2 domain-containing leukocyte protein of 76 kDa) adapter protein is expressed in T cells and myeloid cells, whereas its homologue 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, FcvarepsilonRI and gpVI collagen receptor signaling, and participates in signaling via FcgammaR and killer cell inhibitory receptors. BLNK plays a critical role in B cell receptor signaling. We show that murine bone marrow-derived macrophages express both SLP-76 and BLNK. Selective ligation of FcgammaRI and FcgammaRII/III resulted in tyrosine phosphorylation of both SLP-76 and BLNK. SLP-76(-/-) bone marrow-derived macrophages display FcgammaR-mediated tyrosine phosphorylation of Syk, phospholipase C-gamma2, and extracellular signal regulated kinases 1 and 2, and normal FcgammaR-dependent phagocytosis. These data suggest that both SLP-76 and BLNK are coupled to FcgammaR signaling in murine macrophages.
authors.affiliation: Division of Immunology, Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: F A
authors.initials: FA
authors.lastname: Bonilla
authors.forename: R M
authors.initials: RM
authors.lastname: Fujita
authors.forename: V I
authors.initials: VI
authors.lastname: Pivniouk
authors.forename: A C
authors.initials: AC
authors.lastname: Chan
authors.forename: R S
authors.initials: RS
authors.lastname: Geha
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D003432:Cross-Linking Reagents; D005434:Flow Cytometry; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D010587:Phagocytosis; D010750:Phosphoproteins / Q000172:deficiency / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D017452:Receptors, IgG / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C113939:B cell linker protein; D002352:Carrier Proteins; D003432:Cross-Linking Reagents; D010750:Phosphoproteins; D017452:Receptors, IgG; C092947:SLP-76 signal Transducing adaptor proteins; D014443:Tyrosine