SLP-76 (SH2 domain-containing Leukocyte Protein of 76 kDa) is a tyrosine phosphoprotein that is involved in the T cell receptor (TCR)-mediated intracellular signaling pathway. It may be involved in the signaling pathways of other peripheral blood leukocytes, thymic/splenic cells, and in human T, B, and monocytic cell lines. SLP-76 consists of several motifs that signify its importance in protein-protein interactions involved in intracellular signaling pathways, such as the SH2 domain in the C-terminus, the three amino-terminus 17-amino acid repeats with conserved tyrosine and acidic residues (DYE(S/P)P), and a proline rich region. SLP-76 has been shown to associate with Gads, Grb2, PLCg1, SLAP-130, and Vav, all of which are part of the signaling cascade in T lymphocytes. An early event in the T cell activation pathway is the phosphorylation, by the Syk-family kinase ZAP-70, of SLP-76 at the three conserved tyrosine motifs, which then mediate interactions with downstream effectors. The phosphorylated tyrosine 128 (Y128) brings the Rho family guanine nucleotide exchange factor Vav1 and the Nck adapter protein, which binds to p21-activated kinase (PAK1) and Wiskott-Aldrich syndrome protein (WASP), into the activation complex.
Vav1, PAK1, and WASP may mediate TCR-stimulated actin cytoskeletal rearrangement. The J141-688.36.58 monoclonal antibody recognizes the phosphorylated Y128 of activated SLP-76.