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

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

^*Division of Immunology, Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA 02115; and ^†Howard Hughes Medical Institute, Center for Immunology, and Departments of Medicine and Pathology, Washington University School of Medicine, St. Louis, MO 63110

Communicated by Frederick W. Alt, Harvard Medical School, Boston, MA (received for review August 10, 1999)

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-γ, mitogen-activated protein kinases, and the GTPases Ras and Rho. SLP-76 plays a critical role in T cell receptor, FcɛRI and gpVI collagen receptor signaling, and participates in signaling via FcγR 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 FcγRI and FcγRII/III resulted in tyrosine phosphorylation of both SLP-76 and BLNK. SLP-76^−/− bone marrow-derived macrophages display FcγR-mediated tyrosine phosphorylation of Syk, phospholipase C-γ2, and extracellular signal regulated kinases 1 and 2, and normal FcγR-dependent phagocytosis. These data suggest that both SLP-76 and BLNK are coupled to FcγR signaling in murine macrophages.

Footnotes

↵ ‡ To whom reprint requests should be addressed at: Division of Immunology, Children's Hospital, Enders Building, Room 809, 300 Longwood Avenue, Boston, MA 02115. E-mail: geha{at}a1.tch.harvard.edu.
Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.040543597.
Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.040543597
Abbreviations:

PLC,

phospholipase C;

TCR,

T cell receptor;

FcR,

Fc receptor;

BMM,

bone marrow-derived macrophages;

ERK,

extracellular signal regulated kinase;

BLNK,

B cell linker protein;

SLP-76,

Src homology 2 domain-containing leukocyte protein of 76 kDa;

SRBC,

sheep red blood cells