Tyr128
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Home > Phosphorylation Site Page: > Tyr128  -  SLP76 (human)

Site Information
DGEDDGDyEsPNEEE   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448219

In vivo Characterization
Methods used to characterize site in vivo:
flow cytometry ( 3 , 6 , 7 ) , immunoassay ( 7 ) , immunoprecipitation ( 9 , 10 ) , mass spectrometry ( 6 ) , mutation of modification site ( 6 , 7 , 8 , 9 , 10 , 12 , 13 , 14 , 15 , 16 , 17 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 9 , 10 , 12 , 14 , 15 , 16 ) , western blotting ( 1 , 2 , 4 , 5 , 6 , 7 , 9 , 15 , 16 , 17 )
Disease tissue studied:
leukemia ( 1 , 2 , 4 , 6 , 7 , 8 , 9 ) , T cell leukemia ( 1 , 2 , 4 , 6 , 7 , 8 , 9 ) , mastocytoma ( 9 )
Relevant cell line - cell type - tissue:
CD8+ (T lymphocyte) ( 3 ) , HEK293T (epithelial) ( 14 ) , J14.SY ( 7 ) , Jurkat (T lymphocyte) ( 1 , 2 , 4 , 6 , 7 , 8 , 9 , 12 , 13 , 14 , 15 , 16 , 17 ) , lymphocyte-spleen ( 10 ) , natural killer cell ( 9 ) , P116 (T lymphocyte) ( 16 ) , P815 (mast) ( 9 ) , S2 ( 5 , 9 ) , T lymphocyte ( 7 ) , thymocyte-thymus ( 10 )

Upstream Regulation
Regulatory protein:
CD244 (human) ( 9 ) , CD48 (human) ( 9 ) , DNAM-1 (human) ( 9 ) , FCGR3A (human) ( 9 ) , KLRK1 (human) ( 9 ) , ULBP1 (human) ( 9 )
Putative in vivo kinases:
Syk (human) ( 5 , 14 ) , ZAP70 (human) ( 2 , 15 )
Kinases, in vitro:
Lck (human) ( 17 ) , ZAP70 (human) ( 2 , 17 )
Treatments:
antibody ( 1 , 2 , 7 , 9 , 10 , 12 , 14 , 17 ) , calyculin_A ( 12 ) , CAS_227449-73-2 ( 9 ) , CUE-101 ( 3 ) , CXCL12 ( 7 , 15 ) , piceatannol ( 9 ) , PP2 ( 9 ) , Staphylococcal enterotoxin E ( 4 ) , vanadate ( 14 )

Downstream Regulation
Effects of modification on SLP76:
molecular association, regulation ( 8 , 9 , 13 , 14 ) , phosphorylation ( 10 , 13 , 15 )
Effects of modification on biological processes:
cytoskeletal reorganization ( 7 , 8 ) , signaling pathway regulation ( 2 , 9 ) , transcription, induced ( 7 , 16 )
Induce interaction with:
ITK (human) ( 14 ) , NCK1 (human) ( 8 , 14 ) , PIK3R1 (cow) ( 14 ) , VAV1 (human) ( 8 , 9 , 13 , 14 )

References 

1

Hallumi E, et al. (2021) Itk Promotes the Integration of TCR and CD28 Costimulation through Its Direct Substrates SLP-76 and Gads. J Immunol 206, 2322-2337
33931484   Curated Info

2

Tewari R, Shayahati B, Fan Y, Akimzhanov AM (2021) T cell receptor-dependent S-acylation of ZAP-70 controls activation of T cells. J Biol Chem 296, 100311
33482200   Curated Info

3

Quayle SN, et al. (2020) CUE-101, a Novel E7-pHLA-IL2-Fc Fusion Protein, Enhances Tumor Antigen-Specific T-Cell Activation for the Treatment of HPV16-Driven Malignancies. Clin Cancer Res
31964784   Curated Info

4

Celis-Gutierrez J, et al. (2019) Quantitative Interactomics in Primary T Cells Provides a Rationale for Concomitant PD-1 and BTLA Coinhibitor Blockade in Cancer Immunotherapy. Cell Rep 27, 3315-3330.e7
31189114   Curated Info

5

Fasbender F, et al. (2017) Differential Requirements for Src-Family Kinases in SYK or ZAP70-Mediated SLP-76 Phosphorylation in Lymphocytes. Front Immunol 8, 789
28736554   Curated Info

6

Lugassy J, et al. (2015) Modulation of TCR responsiveness by the Grb2-family adaptor, Gads. Cell Signal 27, 125-34
25452106   Curated Info

7

Smith X, et al. (2013) The Chemokine CXCL12 Generates Costimulatory Signals in T Cells to Enhance Phosphorylation and Clustering of the Adaptor Protein SLP-76. Sci Signal 6, ra65
23901140   Curated Info

8

Pauker MH, et al. (2012) Studying the dynamics of SLP-76, Nck, and Vav1 multimolecular complex formation in live human cells with triple-color FRET. Sci Signal 5, rs3
22534133   Curated Info

9

Kim HS, Long EO (2012) Complementary Phosphorylation Sites in the Adaptor Protein SLP-76 Promote Synergistic Activation of Natural Killer Cells. Sci Signal 5, ra49
22786724   Curated Info

10

Sela M, et al. (2011) Sequential phosphorylation of SLP-76 at tyrosine 173 is required for activation of T and mast cells. EMBO J 30, 3160-72
21725281   Curated Info

11

Sanderson MP, et al. (2010) Syk and Lyn mediate distinct Syk phosphorylation events in FcɛRI-signal transduction: implications for regulation of IgE-mediated degranulation. Mol Immunol 48, 171-8
20828828   Curated Info

12

Di Bartolo V, et al. (2007) A novel pathway down-modulating T cell activation involves HPK-1-dependent recruitment of 14-3-3 proteins on SLP-76. J Exp Med 204, 681-91
17353368   Curated Info

13

Beach D, et al. (2007) Dual role of SLP-76 in mediating T cell receptor-induced activation of phospholipase C-gamma1. J Biol Chem 282, 2937-46
17148460   Curated Info

14

Shim EK, et al. (2004) Association of the Src homology 2 domain-containing leukocyte phosphoprotein of 76 kD (SLP-76) with the p85 subunit of phosphoinositide 3-kinase. FEBS Lett 575, 35-40
15388330   Curated Info

15

Kremer KN, et al. (2003) Distinct role of ZAP-70 and Src homology 2 domain-containing leukocyte protein of 76 kDa in the prolonged activation of extracellular signal-regulated protein kinase by the stromal cell-derived factor-1 alpha/CXCL12 chemokine. J Immunol 171, 360-7
12817019   Curated Info

16

Epler JA, et al. (2000) Regulation of beta 1 integrin-mediated adhesion by T cell receptor signaling involves ZAP-70 but differs from signaling events that regulate transcriptional activity. J Immunol 165, 4941-9
11046020   Curated Info

17

Wardenburg JB, et al. (1996) Phosphorylation of SLP-76 by the ZAP-70 protein-tyrosine kinase is required for T-cell receptor function. J Biol Chem 271, 19641-4
8702662   Curated Info