Product Pathways - Lymphocyte Signaling
Phospho-SLP-76 (Ser376) Antibody #13177
|13177S||100 µl (10 western blots)||---||In Stock||---|
|13177||carrier free and custom formulation / quantity||email request|
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Species cross-reactivity is determined by western blot.
Applications Key: W=Western Blotting
Specificity / Sensitivity
Phospho-SLP-76 (Ser376) Antibody recognizes endogenous levels of SLP-76 protein only when phosphorylated at Ser376. This antibody cross-reacts with a 145 kDa protein of unknown origin.
Source / Purification
Polyclonal antibodies are produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Ser376 of human SLP-76 protein. Antibodies are purified by protein A and peptide affinity chromatography.
Western blot analysis of extracts from EL4 cells, untreated (-) or treated with H2O2 (11 mM, 1 min; +), using Phospho-SLP-76 (Ser376) Antibody (upper) or SLP-76 Antibody #4958 (lower).
SH2 domain-containing leukocyte protein of 76 kDa (SLP-76) is a hematopoietic adapter protein that is important in multiple biochemical signaling pathways and necessary for T cell development and activation (1). ZAP-70 phosphorylates SLP-76 and LAT as a result of TCR ligation. SLP-76 has amino-terminal tyrosine residues followed by a proline rich domain and a carboxy-terminal SH2 domain. Phosphorylation of Tyr113 and Tyr128 result in recruitment of the GEF Vav and the adapter protein Nck (2). TCR ligation also mediates an association between SLP-76 and Itk, which is accomplished in part via the proline rich domain of SLP-76 and the SH3 domain of ITK. Furthermore, the proline rich domain of SLP-76 binds to the SH3 domains of Grb2-like adapter Gads (3-4). In resting cells, SLP-76 is predominantly in the cytosol. Upon TCR ligation, SLP-76 translocates to the plasma membrane and promotes the assembly of a multi-protein signaling complex that includes Vav, Nck, Itk and PLCg1 (1). The expression of SLP-76 is tightly regulated: the protein is detected at very early stages of thymocyte development, increases as thymocyte maturation progresses, and is reduced as cells mature to CD4+ CD8+ double-positive thymocytes (5).
Following TCR ligation, SLP-76 is phosphorylated at Ser376 by the hematopoietic progenitor kinase 1 (HPK1) (6,7). This phosphorylation induces interaction with 14-3-3ε, which leads to the disassembly of TCR signaling complexes and down regulation of TCR signaling (6-8).
- Clements, J.L. (2003) Immunol Rev 191, 211-9.
- Bubeck Wardenburg, J. et al. (1998) Immunity 9, 607-16.
- Bunnell, S.C. et al. (2000) J Biol Chem 275, 2219-30.
- Liu, S.K. et al. (1999) Curr Biol 9, 67-75.
- Clements, J.L. et al. (1998) J Immunol 161, 3880-9.
- Shui, J.W. et al. (2007) Nat Immunol 8, 84-91.
- Di Bartolo, V. et al. (2007) J Exp Med 204, 681-91.
- Lasserre, R. et al. (2011) J Cell Biol 195, 839-53.
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