Affinage

LCP2

Lymphocyte cytosolic protein 2 · UniProt Q13094

Length
533 aa
Mass
60.2 kDa
Annotated
2026-04-28
100 papers in source corpus 55 papers cited in narrative 54 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLP-76 (LCP2) is a hematopoietic-specific multi-domain scaffold protein that nucleates signalosome assembly downstream of ITAM-containing receptors (TCR, FcεRI, FcγR, GPVI, CLEC-2) and integrins in T cells, platelets, mast cells, NK cells, and neutrophils. ZAP-70/Syk phosphorylates SLP-76 at N-terminal tyrosines Y112, Y128, and Y145, creating docking sites for Vav1 and Nck (Y112/Y128) and ITK (Y145), thereby coordinating PLC-γ1/γ2 activation, Ca²⁺ mobilization, Ras/ERK signaling, NF-AT transcription, and actin cytoskeleton remodeling via WASP/Arp2/3 (PMID:8892604, PMID:16456002, PMID:17420479, PMID:9846482). SLP-76 is constitutively bridged to LAT-containing membrane microdomains through Gads binding to a central RxxK motif, and it additionally recruits ADAP via its C-terminal SH2 domain to drive integrin activation and microcluster oligomerization (PMID:11239162, PMID:23979596, PMID:19667077). SLP-76 is negatively regulated by HPK1-mediated S376 phosphorylation, which recruits 14-3-3 proteins and triggers K30 ubiquitination and proteasomal degradation, and by SHP-1-mediated dephosphorylation downstream of inhibitory receptors; SLP-76 knockout in mice causes a complete block in T cell development and defective blood-lymphatic vascular separation through platelet CLEC-2/PDPN signaling (PMID:17353368, PMID:22902619, PMID:9765283, PMID:9665885, PMID:20363774).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1995 High

    Molecular cloning of SLP-76 established the existence of a novel hematopoietic adaptor protein with an SH2 domain capable of engaging tyrosine-phosphorylated signaling partners including PLC-γ1-associated proteins, opening the question of its receptor context and upstream regulation.

    Evidence Cloning from IL-2-stimulated T cells with GST pulldown and co-immunoprecipitation

    PMID:7706237

    Open questions at the time
    • Identity of the 62 kDa and 130 kDa SH2 domain-associated proteins unknown
    • Upstream kinase not identified
    • In vivo function unknown
  2. 1996 High

    Identification of ZAP-70 as the kinase phosphorylating SLP-76 at Y113, Y128, and Y145, and discovery that phospho-SLP-76 recruits Vav via its SH2 domain to synergistically activate NF-AT, established SLP-76 as a TCR-proximal signaling node linking receptor engagement to transcription factor activation and identified the key phosphotyrosine residues.

    Evidence In vitro kinase assays, site-directed mutagenesis, NF-AT reporter assays, co-immunoprecipitation in Jurkat T cells

    PMID:8673706 PMID:8702662 PMID:8892604

    Open questions at the time
    • Which tyrosine recruits which effector not yet resolved
    • In vivo requirement for SLP-76 not tested
  3. 1998 High

    Genetic knockout of SLP-76 revealed it is essential for T cell development (complete thymopoiesis block), platelet collagen-receptor signaling (PLC-γ2 activation, aggregation), and that SLP-76 organizes a trimolecular complex with Nck and Vav to activate PAK1 and actin polymerization, transforming the view of SLP-76 from a simple adaptor to a multifunctional signalosome scaffold.

    Evidence SLP-76 KO mice (two independent labs), platelet aggregation/degranulation assays, co-IP and PAK1 kinase assays

    PMID:9665885 PMID:9695951 PMID:9846482 PMID:9884330

    Open questions at the time
    • Mechanism of SLP-76 membrane recruitment unknown
    • Role in other hematopoietic lineages not yet explored
  4. 1999 High

    Discovery that Gads constitutively bridges SLP-76 to LAT and identification of ADAP (SLAP-130), HPK1, and Nck as SLP-76 SH2 domain or phosphotyrosine-dependent interactors expanded the signalosome model and revealed that SLP-76 serves as a hub integrating both positive (Nck, Vav) and negative (HPK1, ADAP) regulators.

    Evidence Co-IP and domain mapping in T cells and mast cells, NF-AT reporter assays, yeast two-hybrid, SLP-76 KO mast cell functional assays

    PMID:10021361 PMID:10229072 PMID:10377180 PMID:11487585 PMID:9115214

    Open questions at the time
    • Structural basis of Gads-SLP-76 interaction unknown
    • Mechanism of HPK1-mediated negative regulation unclear
  5. 2000 High

    Demonstrating that SLP-76 recruitment to glycolipid-enriched membrane microdomains (GEMs) is essential for TCR signaling and that SLP-76 coordinates actin remodeling via WASP/ADAP/Ena-VASP at the immunological synapse established the spatial dimension of SLP-76 function.

    Evidence LAT/SLP-76 chimeric protein reconstitution in LAT-deficient cells, GEM fractionation, confocal imaging of T cell-APC contacts

    PMID:10747096 PMID:11015445 PMID:11113155

    Open questions at the time
    • Dynamic behavior of SLP-76 at the synapse not resolved
    • How integrin signals feed into SLP-76 not clear
  6. 2001 High

    Mapping of a direct SLP-76–PLC-γ1 SH3 domain interaction via a proline-rich P-1 region and confirmation that GADS KO uncouples SLP-76 from LAT completed the minimal wiring diagram of the LAT-Gads-SLP-76-PLC-γ1 signalosome.

    Evidence GADS KO mice with co-IP, SLP-76 domain mutagenesis and reconstitution in SLP-76-deficient cells, functional reporter assays

    PMID:11239162 PMID:11390650

    Open questions at the time
    • Quantitative affinity requirements for each interaction not defined
    • Stoichiometry of the complex unknown
  7. 2003 High

    Crystal and NMR structures of the Gads C-SH3/SLP-76 RSTK peptide complex revealed a novel non-proline-based SH3 recognition mode (3₁₀ helix), providing the first atomic-level understanding of a key SLP-76 interaction; separately, blood-lymphatic separation failure in SLP-76 KO mice disclosed an unexpected developmental role in a hematopoietic cell-autonomous vascular process.

    Evidence X-ray crystallography (1.7 Å), NMR solution structure, bone marrow reconstitution in KO mice, vascular histology

    PMID:12522250 PMID:12620234 PMID:12773374

    Open questions at the time
    • Identity of the hematopoietic cell type mediating vascular separation unknown
    • Full-length SLP-76 structure unavailable
  8. 2005 High

    Live-cell TIRF imaging showed SLP-76 forms dynamic signaling microclusters at TCR contact sites that migrate centripetally; this established that signaling is organized in discrete membrane-associated clusters rather than uniformly distributed, with ZAP-70 co-recruited and signaling correlated with cluster formation.

    Evidence TIRF microscopy with fluorescently tagged SLP-76 and ZAP-70 in T cell-APC conjugates

    PMID:16273097

    Open questions at the time
    • Molecular determinants of microcluster formation not identified
    • Role of ADAP in cluster assembly not yet explored
  9. 2006 High

    Systematic tyrosine mutagenesis resolved the division of labor among SLP-76 N-terminal tyrosines: Y145 recruits ITK for PLC-γ1 phosphorylation, while Y112/Y128 recruit Vav1 and Nck for Ca²⁺ flux and actin reorganization, and the Gads-binding domain delivers PLC-γ1 to membrane microdomains for phosphorylation by ITK.

    Evidence Individual tyrosine-to-phenylalanine mutants in SLP-76-deficient cells and primary T cells, lipid raft fractionation, in vitro ITK kinase assay

    PMID:16456002 PMID:17148460

    Open questions at the time
    • Whether Y145 directly contacts ITK SH2 domain not structurally confirmed
    • Redundancy between Y112 and Y128 not fully resolved
  10. 2007 High

    HPK1 was identified as the kinase phosphorylating SLP-76 S376, which recruits 14-3-3 proteins to attenuate TCR signaling, and SLP-76 was shown to allosterically maintain ITK in its catalytically active conformation, establishing SLP-76 as both a positive allosteric activator and a target of negative feedback.

    Evidence In vitro kinase assays, S376A mutagenesis, RNAi of HPK1, ITK activity reconstitution upon elution/rebinding to SLP-76

    PMID:17353368 PMID:17420479

    Open questions at the time
    • E3 ligase mediating SLP-76 ubiquitination not identified
    • Structural basis for ITK allosteric activation unknown
  11. 2010 High

    Biophysical determination of a 1:2:2 SLP-76/Nck/Vav1 stoichiometry and demonstration that platelet-specific SLP-76 deletion (via PF4-Cre) suffices to cause lymphatic vascular defects via CLEC-2/PDPN signaling resolved both the molecular architecture of the actin-regulatory complex and the cell type responsible for blood-lymphatic separation.

    Evidence Analytical ultracentrifugation, conditional KO mice, platelet-lymphatic endothelial cell co-culture

    PMID:20363774 PMID:20562827

    Open questions at the time
    • Full structural model of the pentameric complex not available
    • Downstream effectors of CLEC-2/SLP-76 in vascular separation not fully mapped
  12. 2012 High

    HPK1-dependent S376 phosphorylation was linked to K30 ubiquitination and proteasomal degradation of SLP-76, completing the negative feedback circuit; in parallel, ADAP was shown to oligomerize SLP-76 via multipoint SH2 domain binding, providing a mechanism for microcluster assembly, and SLP-76 tyrosine phosphorylation was shown to integrate co-activation receptor signals in NK cells.

    Evidence In vitro ubiquitination assays with K30R mutant, analytical ultracentrifugation of ADAP-SLP-76, confocal imaging of microclusters, NK cell reconstitution with tyrosine mutants

    PMID:22786724 PMID:22902619 PMID:23979596

    Open questions at the time
    • Identity of the E3 ubiquitin ligase targeting K30 still unknown
    • Whether ADAP-mediated oligomerization occurs in non-T cells not tested
  13. 2021 High

    Discovery that SLP-76 directly binds the RAGE cytoplasmic tail via its SAM domain to drive p38/ERK/IKK signaling and cytokine release in macrophages extended SLP-76 function beyond ITAM/integrin-receptor pathways to a pattern-recognition receptor axis relevant to sepsis.

    Evidence Co-IP in macrophages, RAGE/SLP-76 genetic deficiency, TAT-SAM peptide inhibition, CLP sepsis model in mice

    PMID:33436632

    Open questions at the time
    • Whether the SAM domain interaction is direct or requires post-translational modification not established
    • Relevance to human sepsis not validated
    • Structural basis of RAGE-SAM interaction unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full-length structure of SLP-76 in complex with its signalosome partners, the identity of the E3 ubiquitin ligase for K30 ubiquitination, and the mechanism by which SLP-76 allosterically activates ITK remain unresolved.
  • No full-length SLP-76 structure available
  • E3 ligase for K30 ubiquitination unidentified
  • Structural mechanism of ITK allosteric activation by SLP-76 unknown
  • Role of SLP-76 SAM-RAGE axis in other inflammatory contexts untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 6
Localization
GO:0005886 plasma membrane 5 GO:0005829 cytosol 2
Pathway
R-HSA-168256 Immune System 7 R-HSA-162582 Signal Transduction 5 R-HSA-109582 Hemostasis 4 R-HSA-1266738 Developmental Biology 3
Partners
FYB1GRAP2HPK1ITKNCK1PLCG1VAV1ZAP70
Complex memberships
LAT-Gads-SLP-76 signalosomeSLP-76/ITK/PLC-γ1 complexSLP-76/Nck/Vav1 trimolecular complex

Evidence

Reading pass · 54 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 SLP-76 (LCP2) was molecularly cloned as a 76 kDa hematopoietic-specific adaptor protein containing a C-terminal SH2 domain; it directly associates with Grb2 via in vitro GST pulldown, and its SH2 domain precipitates tyrosine phosphoproteins from T cell lysates including PLC-γ1-associated proteins. Molecular cloning, GST fusion protein pulldown, co-immunoprecipitation, in vitro translation The Journal of biological chemistry High 7706237
1996 ZAP-70 phosphorylates SLP-76 in vitro and in heterologous cell systems; SLP-76 phosphorylation is diminished when catalytically inactive ZAP-70 is expressed. SLP-76 overexpression hyperactivates the TCR, while a non-phosphorylatable SLP-76 attenuates signaling. The SH2 domain of SLP-76 is independently required for TCR function. In vitro kinase assay, dominant-negative ZAP-70 expression, overexpression/mutagenesis in T cell lines, reporter gene assay The Journal of biological chemistry High 8702662
1996 SLP-76 directly associates with Vav via the Vav SH2 domain binding to phosphorylated SLP-76; co-overexpression of Vav and SLP-76 synergistically induces NF-AT activation, placing SLP-76 in a complex with Vav during TCR signaling. Co-immunoprecipitation, overexpression, NF-AT reporter assay in Jurkat cells Immunity High 8673706
1996 TCR engagement leads to tyrosine phosphorylation of SLP-76 at its N-terminal acidic region; tyrosines Y113 and Y128 (YESP motifs) and Y145 are phosphorylated, with Y145 being the most important for NF-AT promoter activity. Site-directed mutagenesis, TCR stimulation, NF-AT reporter assay in Jurkat cells Journal of immunology High 8892604
1996 SLP-76 is required for optimal TCR-induced activation of PLC-γ1 and Ras pathways; an SLP-76-deficient T cell line showed that SLP-76 is not required for general tyrosine phosphorylation but is specifically required for PLC-γ1 phosphorylation and TCR-inducible gene expression. SLP-76-deficient cell line (genetic loss), phosphorylation assays, gene expression reporter Science High 9665884
1996 Grb2 constitutively associates with unphosphorylated SLP-76; the SH2 domain of SLP-76 associates with 62 kDa and 130 kDa tyrosine-phosphorylated proteins and a serine/threonine kinase after TCR stimulation. Co-immunoprecipitation, GST-SH2 domain pulldown, in vitro binding The Journal of experimental medicine Medium 8666952
1996 SHP-1 constitutively associates with SLP-76 in B cells via SHP-1 SH2 domains; BCR ligation induces tyrosine phosphorylation of SLP-76 and SHP-1. Co-immunoprecipitation, GST-SH2 domain pulldown, Western blot The Journal of experimental medicine Medium 8760799
1997 ZAP-70 phosphorylates two YESP motifs of SLP-76 (Y113 and Y128) to create binding sites for the Vav SH2 domain; a third motif (Y145, pYEPP) fails to bind Vav SH2. Vav-SLP-76 binding is not absolutely required for IL-2 production in all T cells. In vitro kinase assay, phosphopeptide binding, overexpression in T cell hybridoma Immunity High 9047237
1997 SLAP-130 (FYB/ADAP) is a 130 kDa SLP-76-associated phosphoprotein that interacts via the SH2 domain of SLP-76; overexpression of SLAP-130 negatively regulates TCR-induced IL-2 promoter activity and counteracts SLP-76 augmentation of signaling. Molecular cloning, co-immunoprecipitation with SH2 domain, reporter gene assay The Journal of biological chemistry Medium 9115214
1997 SLP-76 function requires three distinct protein-interaction domains (N-terminal tyrosine-containing acidic region, proline-rich region, C-terminal SH2 domain) for optimal augmentation of TCR-induced NF-AT activity and ERK activation. Domain deletion mutagenesis, overexpression in Jurkat cells, reporter gene assay, kinase assay Journal of immunology Medium 9257823
1998 SLP-76 is required for normal T cell development; SLP-76-null mice have a complete block in thymopoiesis at an early stage with no peripheral T cells, establishing SLP-76 as an essential signal transducer for pre-TCR signaling. Targeted gene knockout in mice, flow cytometry of thymic populations Science High 9665885 9695951
1998 SLP-76 interacts with Nck (an adaptor protein) and Vav (a GEF for Rho-family GTPases), forming a trimolecular complex that activates PAK1 (p21-activated kinase 1) and facilitates actin polymerization downstream of the TCR. Co-immunoprecipitation, PAK1 kinase assay, actin polymerization assay Immunity High 9846482
1998 SLP-76 is a direct substrate of SHP-1 in T cells and NK cells; SHP-1, recruited to killer cell inhibitory receptors, dephosphorylates SLP-76, and tyrosine-phosphorylated SLP-76 is required for optimal cytotoxic lymphocyte activation. Direct binding assay (SHP-1 catalytic domain on SLP-76), functional inhibitory receptor co-engagement assays The Journal of biological chemistry Medium 9765283
1998 SLP-76 is required for optimal PLC-γ2 activation in platelets downstream of the collagen receptor; SLP-76-deficient platelets show impaired collagen-induced platelet aggregation, granule release, and PLC-γ2 tyrosine phosphorylation. SLP-76 KO mouse platelets, platelet aggregation assay, phosphorylation assay, granule release assay The Journal of clinical investigation High 9884330
1999 Gads (Grb2-related adaptor) constitutively interacts with SLP-76 via the C-terminal SH3 domain of Gads and a proline-rich region of SLP-76; Gads also binds tyrosine-phosphorylated LAT via its SH2 domain, bridging LAT and SLP-76 and promoting T cell signaling. Co-immunoprecipitation, domain mapping, NF-AT reporter assay Current biology High 10021361
1999 SLP-76 deficiency in mast cells impairs FcεRI-mediated signaling: SLP-76-null BMMCs fail to release β-hexosaminidase and IL-6, and show reduced PLC-γ1 tyrosine phosphorylation and calcium mobilization after FcεRI cross-linking, while Syk phosphorylation is normal. SLP-76 KO mouse mast cells, degranulation assay, cytokine secretion, phosphorylation assay, calcium flux The Journal of clinical investigation High 10377180
1999 In platelets, tyrosine phosphorylation of SLP-76 by the collagen receptor pathway is downstream of Syk; SLP-76 co-immunoprecipitates with SLAP-130, Vav, Fyn, Lyn, and the FcR γ-chain after collagen stimulation, and SLP-76 deficiency abrogates PLC-γ2 phosphorylation and Ca2+ mobilization. Syk-deficient platelet analysis, co-immunoprecipitation, in vitro kinase assay, calcium mobilization The Journal of biological chemistry High 10026222
1999 Nck SH2 domain interacts with tyrosine-phosphorylated SLP-76 in activated T cells; phosphopeptides corresponding to Y113 and Y128 of SLP-76 compete binding of SLP-76 to the Nck SH2 domain. Co-immunoprecipitation, phosphopeptide competition, in vitro binding European journal of immunology Medium 10229072
1999 FYN-T selectively phosphorylates FYB/SLAP, creating binding sites for the SH2 domains of FYN-T and SLP-76; co-expression of FYN-T, FYB, and SLP-76 synergistically up-regulates IL-2 transcription via TCR ligation. In vitro kinase assay, co-immunoprecipitation, NF-AT/IL-2 reporter assay The Journal of biological chemistry Medium 10409671
1999 SLP-76 SH2 domain binds HPK1 at Tyr379; HPK1 interacts with SLP-76 in T cells and inhibits AP-1 activation in an SLP-76 SH2-domain-dependent manner, integrating HPK1 into antigen receptor signaling cascades. Yeast two-hybrid, co-immunoprecipitation, reporter gene assay, homology modeling The Journal of biological chemistry Medium 11487585
1999 GrpL (Grb2-related adaptor) co-immunoprecipitates with SLP-76 but not with Sos1/2 in Jurkat cells; GrpL cooperates with SLP-76 to augment NF-AT activation, defining a distinct Grb2-like adaptor complex with SLP-76. Co-immunoprecipitation, NF-AT reporter assay The Journal of experimental medicine Medium 10209041
2000 Fyb/SLAP (FYB/ADAP) links TCR signaling to actin cytoskeleton remodeling by acting as a ligand for Ena/VASP EVH1 domains; upon TCR engagement, Fyb/SLAP localizes to the T cell-APC interface within complexes containing WASP, Nck, and SLP-76. Co-immunoprecipitation, confocal microscopy, WASP/Arp2/3 inhibition, biochemical fractionation The Journal of cell biology High 10747096
2000 SLP-76 recruitment to glycolipid-enriched membrane microdomains (GEMs) requires amino acids 224-244 of SLP-76 and is critical for TCR signaling; forced membrane localization of SLP-76 via a LAT/SLP-76 chimera reconstitutes PLC-γ1 phosphorylation, ERK activation, and NF-AT activity in LAT-deficient cells. Chimeric protein expression, fractionation into GEMs, reporter gene assay, phosphorylation assays The Journal of experimental medicine High 11015445
2000 SLP-76 relays signals from platelet integrin αIIbβ3 to the actin cytoskeleton: fibrinogen binding triggers Syk-dependent SLP-76 phosphorylation, which promotes SLP-76 association with Nck and Vav1, lamellipodia formation, and PAK kinase activation. CHO cell expression system, co-immunoprecipitation, PAK kinase assay, microscopy The Journal of biological chemistry High 11113155
2001 SLP-76 directly interacts with the SH3 domain of PLC-γ1 via a proline-rich 'P-1 domain' (67 amino acids); this interaction is constitutive and required for TCR-mediated ERK, PLC-γ1, and NF-AT activation. The Gads-binding domain of SLP-76 mediates inducible recruitment to a PLC-γ1-LAT complex. Mutagenesis, co-immunoprecipitation, reporter gene assay, reconstitution in SLP-76-deficient cells Molecular and cellular biology High 11390650
2001 SLAP-130 (FYB/ADAP) interaction with SLP-76 requires phospho-Y559 of SLAP-130; this interaction is important for the negative regulatory role of SLAP-130, specifically inhibiting TCR-induced ERK activation but not PLC-γ1 phosphorylation. Mutagenesis, co-immunoprecipitation, ERK activation assay, NF-AT reporter assay The Journal of biological chemistry Medium 10671560
2001 WASP recruitment to the T cell-APC contact site requires Nck (via WASP proline-rich domain), while WASP activation requires Vav-1 for localized Cdc42 activation; SLP-76 coordinates both events by acting as a scaffold bringing Nck and WASP near Vav-1/Cdc42-GTP. Vav-1-deficient T cells, microscopy of WASP localization, co-immunoprecipitation, Cdc42 activation assay Journal of immunology High 12874226
2001 GADS is required for coupling SLP-76 to LAT in T cells; GADS-deficient thymocytes fail to respond to CD3 cross-linking and the association between SLP-76 and LAT is uncoupled, establishing GADS as the physical bridge between SLP-76 and LAT. GADS KO mice, co-immunoprecipitation, thymocyte proliferation assay, in vivo selection assays Science High 11239162
2001 SLP-76 mediates signaling via Fcγ receptors and integrins in neutrophils; SLP-76-deficient neutrophils show decreased FcγR-induced calcium flux and reactive oxygen intermediate production, and fail to produce ROI, spread, or activate key downstream regulators upon integrin ligation. SLP-76 KO mouse neutrophils, calcium flux, ROI production assay, spreading assay Immunity High 14614862
2002 The RxxK motif in SLP-76 (R237 and K240) mediates high-affinity binding to the C-terminal SH3 domain of Gads; single point mutations in R237 or K240 abrogate SLP-76/Gads association in vivo and impair SLP-76 function in TCR signaling. Peptide array, in vitro binding (Kd measurement), site-directed mutagenesis, co-immunoprecipitation, NF-AT reporter assay Current biology High 12176364
2003 Crystal structure (1.7 Å) of the Mona/Gads C-terminal SH3 domain complexed with a SLP-76 peptide reveals a novel non-proline-type II helix binding mode: the SLP-76 RSTK peptide forms a 3(10) helix inserting into a negatively charged double pocket on the SH3 domain. X-ray crystallography (1.7 Å resolution), mutagenesis, in vitro binding The EMBO journal High 12773374
2003 NMR solution structure of the Gads C-terminal SH3 domain in complex with an SLP-76 RSTK-containing peptide shows the peptide adopts a right-handed 3(10) helix at the RSTK locus engaging four distinct binding pockets, confirming a novel mode of SH3 recognition. NMR structure determination, mutagenesis, peptide binding assay Molecular cell High 12620234
2003 SLP-76 deficiency causes failure of blood-lymphatic vascular separation in mice; SLP-76 is required in hematopoietic cells (not endothelial cells) for this separation, as bone marrow reconstitution with SLP-76-deficient cells confers blood-filled lymphatics in wild-type mice. SLP-76 KO mice, bone marrow reconstitution, vascular histology Science High 12522250
2004 ADAP binding to SLP-76 differentially regulates peripheral SMAC (pSMAC) formation at the immunological synapse versus T cell-APC conjugation; ADAP-SLP-76 interaction requires specific YDDV sites of ADAP, and loss of this interaction acts as a dominant negative on pSMAC formation and IL-2 production. Mutagenesis of ADAP, immunological synapse imaging, IL-2 production assay, LFA-1 clustering assay The Journal of experimental medicine Medium 15477347
2005 TCR-activated reactive oxygen species (ROS) induce transient oxidative inactivation of SHP-2 (but not SHP-1); SHP-2 is recruited to the LAT-Gads-SLP-76 complex and directly regulates phosphorylation of Vav1 and ADAP, with the ADAP-SLP-76 association regulated by SHP-2 in a redox-dependent manner. ROS detection, phosphatase activity assay, co-immunoprecipitation, T cell adhesion assay The EMBO journal Medium 15933714
2005 SLP-76 forms signaling microclusters at TCR contact sites with APCs containing ZAP-70; microclusters are continuously generated at the periphery, migrate toward the central SMAC, and tyrosine phosphorylation and calcium influx occur as microclusters form. Inhibition of signaling prevents ZAP-70 recruitment into microclusters. Live-cell imaging (TIRF microscopy), fluorescently-tagged SLP-76 and ZAP-70, signaling inhibitors Nature immunology High 16273097
2005 CD6 cytoplasmic tail phospho-Y662 directly binds the SH2 domain of SLP-76 (Kd = 0.5 µM at 37°C); this interaction is required for CD6-mediated T cell costimulation. Phosphopeptide binding (equilibrium dissociation constant measured), co-immunoprecipitation, mutagenesis, costimulation assay Molecular and cellular biology High 16914752
2006 SLP-76 forms dynamic membrane clusters upon FcεRI cross-linking in mast cells, colocalizing with FcεRI, Syk, LAT, and phosphotyrosine; disruption of the SLP-76-Gads interaction (by SLP-76 mutation) prevents translocation and clustering, inhibiting calcium flux, degranulation, and cytokine secretion. Confocal real-time imaging, mutagenesis of SLP-76 Gads-binding region, calcium flux, degranulation assay Molecular and cellular biology High 16479002
2006 SLP-76 Tyr145 is the most critical N-terminal tyrosine for T cell development and function; Y145 is required for optimal association of SLP-76 with ITK, while Y112/Y128 associate with Vav and Nck and are required for TCR-induced Ca2+ flux and actin reorganization. Individual tyrosine mutagenesis in reconstituted SLP-76-deficient cells and primary T cells, calcium flux, actin assay, co-immunoprecipitation Journal of immunology High 16456002
2006 The Gads-binding domain of SLP-76 is required for PLC-γ1 recruitment to GEMs, while the N-terminal tyrosine phosphorylation sites and P-1 region are required for PLC-γ1 phosphorylation at Y783; ITK (associated with SLP-76 via N-terminal tyrosines) efficiently phosphorylates PLC-γ1 at Y783 in vitro. Lipid raft fractionation, PLC-γ1 phosphorylation assay, in vitro kinase assay with ITK, mutagenesis The Journal of biological chemistry High 17148460
2007 HPK1 phosphorylates SLP-76 at serine 376; this serine phosphorylation mediates recruitment of 14-3-3ε and ζ proteins to SLP-76, which attenuates TCR-induced tyrosine phosphorylation of SLP-76 and PLC-γ1 and reduces IL-2 transcription. S376A mutation or HPK-1 knockdown enhances TCR signaling. RNAi knockdown, in vitro phosphorylation, mutagenesis (S376A), co-immunoprecipitation, IL-2 reporter assay, phosphorylation assay The Journal of experimental medicine High 17353368
2007 SLP-76 is required for TCR-induced activation of ITK; ITK bound to SLP-76 represents most of the catalytically active ITK, and ITK activity is lost upon mild elution from the SLP-76 complex but restored upon reconstitution. SLP-76 N-terminal tyrosines are required for ITK activation but not ZAP-70 activation. In vitro kinase assay (ITK vs ZAP-70 on PLC-γ1), co-immunoprecipitation, mutagenesis, reconstitution experiments Proceedings of the National Academy of Sciences High 17420479
2007 The Gads C-SH3 domain binds the SLP-76 RxxK motif with very high affinity (Kd = 8-20 nM); T cell signaling efficiency declines with decreasing Gads-SLP-76 binding affinity, demonstrating a quantitative affinity requirement for efficient TCR signaling. Quantitative affinity measurement, SLP-76 mutants with graded affinities, TCR signaling reporter assays in Jurkat cells The EMBO journal High 17235283
2008 SLP-76 N-terminal tyrosines Y145 and Y112-128 are required for thymocyte selection but can complement one another in trans (on separate SLP-76 molecules); Y145 differentially supports Itk-dependent pathways while Y112-128 supports Vav1 phosphorylation, demonstrating cooperativity between SLP-76 molecules. Knock-in mice (Y145F and Y112-128F), compound heterozygote analysis, phosphorylation assays, co-immunoprecipitation Immunity High 18342008
2008 VLA-4 integrin costimulation retards actin-driven inward flows and prevents centralization of SLP-76 microclusters, prolonging lateral SLP-76/ZAP-70 interactions and retaining SLP-76 in tyrosine-phosphorylated peripheral structures, thereby sustaining T cell signaling. Live TIRF microscopy of SLP-76 microclusters, integrin ligand modulation, actin flow measurement Immunity High 18549800
2009 SLP-76 mediates 'outside-in' integrin signaling in T cells; SLP-76 relocalizes to integrin-initiated microclusters by a mechanism requiring ADAP binding (not LAT/Gads), distinct from TCR-initiated microcluster assembly, and is required for T cell adhesion to integrin ligands. SLP-76 KO T cells, domain mutagenesis (ADAP-binding vs Gads-binding mutants), microcluster imaging, adhesion assay Molecular and cellular biology High 19667077
2010 The SLP-76/Nck/VAV1 complex has defined stoichiometry (one SLP-76, two Nck, two VAV1); a direct Nck-VAV1 interaction via the C-terminal SH3 domain of Nck and the VAV1 N-terminal SH3 domain is required for actin polymerization after T cell activation. Analytical ultracentrifugation, co-immunoprecipitation, mutagenesis of Nck-VAV1 interface, actin polymerization assay The EMBO journal High 20562827
2010 Platelet CLEC-2 receptors bind lymphatic endothelial PDPN and activate SLP-76 signaling; platelet-specific deletion of SLP-76 (via PF4-Cre) is sufficient to cause lymphatic vascular defects, and SLP-76-dependent platelet aggregate formation occurs on lymphatic endothelial cell surfaces. Conditional KO (PF4-Cre x Slp76 flox), in vivo and ex vivo vascular imaging, platelet-LEC co-culture Blood High 20363774
2012 HPK1-dependent serine 376 phosphorylation of SLP-76 mediates ubiquitination of SLP-76 at lysine 30, targeting phosphorylated SLP-76 for proteasomal degradation during TCR signaling; K30R mutation enhances anti-CD3-induced ERK and JNK activation. In vitro ubiquitination assay, mutagenesis (S376A, K30R), proteasome inhibition, ERK/JNK activation assay The Journal of biological chemistry High 22902619
2012 In NK cells, SLP-76 Y113 and Y128 are phosphorylated by distinct co-activation receptor pairs (e.g., NKG2D and 2B4), enabling SLP-76 binding to Vav1; combined phosphorylation of both tyrosines is required for synergistic Ca2+ mobilization and NK cell activation. SLP-76 KD and reconstitution with tyrosine mutants, Ca2+ flux assay, cytotoxicity assay, co-immunoprecipitation Science signaling High 22786724
2012 SLP-76 and ADAP are required for E-selectin-mediated integrin activation and slow leukocyte rolling in neutrophils; two N-terminal tyrosines and the SH2 domain of SLP-76 are required for downstream signaling, placing BTK and then PI3Kγ/PLCγ2 downstream of SLP-76 in this pathway. Genetically engineered KO mice, transduced primary leukocytes, intravital microscopy, kinase assays The Journal of experimental medicine High 22291096
2012 SLP-76, Nck, and Vav1 form a trimolecular complex in live T cells; Nck-Vav1 dimers are constitutively formed independently of T cell activation and SLP-76-Nck association; after TCR stimulation, SLP-76 phosphorylation enables Nck binding and complex assembly. The Nck-Vav1 interaction requires Vav1 proline-rich/SH3 domain and is critical for actin rearrangement. Triple-color FRET (3FRET) in live T cells, mutagenesis of Vav1 SH3, actin rearrangement assay Science signaling High 22534133
2013 ADAP contains three binding sites for the SLP-76 SH2 domain; multipoint binding of SLP-76 to ADAP oligomerizes SLP-76 SH2 domain in vitro and is critical for SLP-76 microcluster assembly in stimulated T cells; any combination of two sites partially restores microclusters. Analytical ultracentrifugation, biophysical binding assays, confocal imaging of microclusters, ADAP mutagenesis, functional T cell assays Molecular and cellular biology High 23979596
2021 SLP-76 directly binds the cytosolic tail of RAGE via its SAM (sterile α motif) domain; this interaction mediates downstream p38 MAPK, ERK1/2, and IKKα/β phosphorylation as well as cytokine release in macrophages. TAT-SAM peptide delivery blocks RAGE-SLP-76 interaction and attenuates sepsis in mice. Co-immunoprecipitation in vitro and in vivo, genetic deficiency of RAGE/SLP-76, TAT-peptide cell delivery, CLP sepsis model Nature communications High 33436632

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Newly generated T cell receptor microclusters initiate and sustain T cell activation by recruitment of Zap70 and SLP-76. Nature immunology 566 16273097
1998 Uncoupling of nonreceptor tyrosine kinases from PLC-gamma1 in an SLP-76-deficient T cell. Science (New York, N.Y.) 342 9665884
1998 Requirement for the leukocyte-specific adapter protein SLP-76 for normal T cell development. Science (New York, N.Y.) 340 9665885
2010 Platelets regulate lymphatic vascular development through CLEC-2-SLP-76 signaling. Blood 332 20363774
2003 Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk. Science (New York, N.Y.) 321 12522250
1996 Phosphorylation of SLP-76 by the ZAP-70 protein-tyrosine kinase is required for T-cell receptor function. The Journal of biological chemistry 311 8702662
1998 Impaired viability and profound block in thymocyte development in mice lacking the adaptor protein SLP-76. Cell 302 9695951
1995 Molecular cloning of SLP-76, a 76-kDa tyrosine phosphoprotein associated with Grb2 in T cells. The Journal of biological chemistry 288 7706237
1996 Vav and SLP-76 interact and functionally cooperate in IL-2 gene activation. Immunity 286 8673706
1999 The hematopoietic-specific adaptor protein gads functions in T-cell signaling via interactions with the SLP-76 and LAT adaptors. Current biology : CB 254 10021361
2000 Fyn-binding protein (Fyb)/SLP-76-associated protein (SLAP), Ena/vasodilator-stimulated phosphoprotein (VASP) proteins and the Arp2/3 complex link T cell receptor (TCR) signaling to the actin cytoskeleton. The Journal of cell biology 246 10747096
2006 SLP76 and SLP65: complex regulation of signalling in lymphocytes and beyond. Nature reviews. Immunology 221 16493428
1997 Molecular cloning of SLAP-130, an SLP-76-associated substrate of the T cell antigen receptor-stimulated protein tyrosine kinases. The Journal of biological chemistry 213 9115214
1998 Regulation of PAK activation and the T cell cytoskeleton by the linker protein SLP-76. Immunity 202 9846482
1997 Regulation of Vav-SLP-76 binding by ZAP-70 and its relevance to TCR zeta/CD3 induction of interleukin-2. Immunity 189 9047237
1996 Implication of the GRB2-associated phosphoprotein SLP-76 in T cell receptor-mediated interleukin 2 production. The Journal of experimental medicine 167 8666952
2001 Evidence for a molecular complex consisting of Fyb/SLAP, SLP-76, Nck, VASP and WASP that links the actin cytoskeleton to Fcgamma receptor signalling during phagocytosis. Journal of cell science 164 11739662
2001 Identification of a phospholipase C-gamma1 (PLC-gamma1) SH3 domain-binding site in SLP-76 required for T-cell receptor-mediated activation of PLC-gamma1 and NFAT. Molecular and cellular biology 163 11390650
1996 p95vav associates with tyrosine-phosphorylated SLP-76 in antigen-stimulated T cells. The Journal of experimental medicine 163 9064333
1999 Fetal hemorrhage and platelet dysfunction in SLP-76-deficient mice. The Journal of clinical investigation 146 9884330
1999 SLP-76 deficiency impairs signaling via the high-affinity IgE receptor in mast cells. The Journal of clinical investigation 139 10377180
2003 SLP-76 coordinates Nck-dependent Wiskott-Aldrich syndrome protein recruitment with Vav-1/Cdc42-dependent Wiskott-Aldrich syndrome protein activation at the T cell-APC contact site. Journal of immunology (Baltimore, Md. : 1950) 125 12874226
2001 Requirement for the SLP-76 adaptor GADS in T cell development. Science (New York, N.Y.) 116 11239162
2003 Structural basis for specific binding of the Gads SH3 domain to an RxxK motif-containing SLP-76 peptide: a novel mode of peptide recognition. Molecular cell 115 12620234
2008 T cell costimulation via the integrin VLA-4 inhibits the actin-dependent centralization of signaling microclusters containing the adaptor SLP-76. Immunity 113 18549800
1996 Tyrosines 113, 128, and 145 of SLP-76 are required for optimal augmentation of NFAT promoter activity. Journal of immunology (Baltimore, Md. : 1950) 110 8892604
2002 A high-affinity Arg-X-X-Lys SH3 binding motif confers specificity for the interaction between Gads and SLP-76 in T cell signaling. Current biology : CB 106 12176364
1999 GrpL, a Grb2-related adaptor protein, interacts with SLP-76 to regulate nuclear factor of activated T cell activation. The Journal of experimental medicine 103 10209041
1999 Tyrosine phosphorylation of SLP-76 is downstream of Syk following stimulation of the collagen receptor in platelets. The Journal of biological chemistry 101 10026222
2003 Structural basis for SH3 domain-mediated high-affinity binding between Mona/Gads and SLP-76. The EMBO journal 98 12773374
2001 Hematopoietic progenitor kinase 1 associates physically and functionally with the adaptor proteins B cell linker protein and SLP-76 in lymphocytes. The Journal of biological chemistry 97 11487585
2005 Receptor-stimulated oxidation of SHP-2 promotes T-cell adhesion through SLP-76-ADAP. The EMBO journal 95 15933714
2000 Recruitment of SLP-76 to the membrane and glycolipid-enriched membrane microdomains replaces the requirement for linker for activation of T cells in T cell receptor signaling. The Journal of experimental medicine 94 11015445
2012 Crucial role of SLP-76 and ADAP for neutrophil recruitment in mouse kidney ischemia-reperfusion injury. The Journal of experimental medicine 92 22291096
2000 The molecular adapter SLP-76 relays signals from platelet integrin alphaIIbbeta3 to the actin cytoskeleton. The Journal of biological chemistry 92 11113155
1998 SLP-76 is a direct substrate of SHP-1 recruited to killer cell inhibitory receptors. The Journal of biological chemistry 92 9765283
2010 Cooperative interactions at the SLP-76 complex are critical for actin polymerization. The EMBO journal 90 20562827
2007 A novel pathway down-modulating T cell activation involves HPK-1-dependent recruitment of 14-3-3 proteins on SLP-76. The Journal of experimental medicine 89 17353368
2001 The C-terminal SH3 domain of the adapter protein Grb2 binds with high affinity to sequences in Gab1 and SLP-76 which lack the SH3-typical P-x-x-P core motif. Oncogene 88 11314042
1999 FYN-T-FYB-SLP-76 interactions define a T-cell receptor zeta/CD3-mediated tyrosine phosphorylation pathway that up-regulates interleukin 2 transcription in T-cells. The Journal of biological chemistry 88 10409671
2006 Syk and Slp-76 mutant mice reveal a cell-autonomous hematopoietic cell contribution to vascular development. Developmental cell 87 16950126
2008 Complementation in trans of altered thymocyte development in mice expressing mutant forms of the adaptor molecule SLP76. Immunity 86 18342008
2001 A PAK1-PIX-PKL complex is activated by the T-cell receptor independent of Nck, Slp-76 and LAT. The EMBO journal 86 11157752
2001 Differential requirement for SLP-76 domains in T cell development and function. Immunity 84 11754821
1999 Association of Nck with tyrosine-phosphorylated SLP-76 in activated T lymphocytes. European journal of immunology 83 10229072
1998 Molecular interaction between the Fyn-associated protein SKAP55 and the SLP-76-associated phosphoprotein SLAP-130. The Journal of biological chemistry 83 9748251
2006 CD6 regulates T-cell responses through activation-dependent recruitment of the positive regulator SLP-76. Molecular and cellular biology 80 16914752
2001 CD28 signaling via VAV/SLP-76 adaptors: regulation of cytokine transcription independent of TCR ligation. Immunity 80 11754814
2004 ADAP-SLP-76 binding differentially regulates supramolecular activation cluster (SMAC) formation relative to T cell-APC conjugation. The Journal of experimental medicine 77 15477347
1999 Perturbed regulation of ZAP-70 and sustained tyrosine phosphorylation of LAT and SLP-76 in c-Cbl-deficient thymocytes. Journal of immunology (Baltimore, Md. : 1950) 77 10358158
2007 SLP-76 mediates and maintains activation of the Tec family kinase ITK via the T cell antigen receptor-induced association between SLP-76 and ITK. Proceedings of the National Academy of Sciences of the United States of America 73 17420479
2004 The SLP-76 family of adapter proteins. Seminars in immunology 73 15541653
2002 Differential requirement for LAT and SLP-76 in GPVI versus T cell receptor signaling. The Journal of experimental medicine 72 11901197
1997 Three domains of SLP-76 are required for its optimal function in a T cell line. Journal of immunology (Baltimore, Md. : 1950) 70 9257823
2000 Involvement of LAT, Gads, and Grb2 in compartmentation of SLP-76 to the plasma membrane. The Journal of experimental medicine 68 10993915
2009 SLP-76-ADAP adaptor module regulates LFA-1 mediated costimulation and T cell motility. Proceedings of the National Academy of Sciences of the United States of America 67 19617540
2005 Dynamic recruitment of PAK1 to the immunological synapse is mediated by PIX independently of SLP-76 and Vav1. Nature immunology 67 15864311
2000 Hematopoietic reconstitution of SLP-76 corrects hemostasis and platelet signaling through alpha IIb beta 3 and collagen receptors. Proceedings of the National Academy of Sciences of the United States of America 67 11050236
1998 SLP-76 expression is restricted to hemopoietic cells of monocyte, granulocyte, and T lymphocyte lineage and is regulated during T cell maturation and activation. Journal of immunology (Baltimore, Md. : 1950) 67 9780153
2003 SLP-76 regulates Fcgamma receptor and integrin signaling in neutrophils. Immunity 65 14614862
2006 Evidence for the requirement of ITAM domains but not SLP-76/Gads interaction for integrin signaling in hematopoietic cells. Molecular and cellular biology 64 16943434
1999 Novel isoform of lymphoid adaptor FYN-T-binding protein (FYB-130) interacts with SLP-76 and up-regulates interleukin 2 production. The Journal of biological chemistry 64 10497204
1999 Cutting edge: SLP-76 cooperativity with FYB/FYN-T in the Up-regulation of TCR-driven IL-2 transcription requires SLP-76 binding to FYB at Tyr595 and Tyr651. Journal of immunology (Baltimore, Md. : 1950) 63 10570256
2012 Complementary phosphorylation sites in the adaptor protein SLP-76 promote synergistic activation of natural killer cells. Science signaling 62 22786724
2004 Roles of the proline-rich domain in SLP-76 subcellular localization and T cell function. The Journal of biological chemistry 61 14722089
2009 The adapter protein SLP-76 mediates "outside-in" integrin signaling and function in T cells. Molecular and cellular biology 60 19667077
2002 Differential role of SLP-76 domains in T cell development and function. Proceedings of the National Academy of Sciences of the United States of America 60 11792851
1997 SLP-76 is a substrate of the high affinity IgE receptor-stimulated protein tyrosine kinases in rat basophilic leukemia cells. The Journal of biological chemistry 60 8995445
2005 The adaptor molecules LAT and SLP-76 are specifically targeted by Yersinia to inhibit T cell activation. The Journal of experimental medicine 58 15699071
2001 ZAP-70 and SLP-76 regulate protein kinase C-theta and NF-kappa B activation in response to engagement of CD3 and CD28. Journal of immunology (Baltimore, Md. : 1950) 57 11313406
1999 SLP-76 and Vav function in separate, but overlapping pathways to augment interleukin-2 promoter activity. The Journal of biological chemistry 57 10347175
1999 Evidence that phospholipase C-gamma2 interacts with SLP-76, Syk, Lyn, LAT and the Fc receptor gamma-chain after stimulation of the collagen receptor glycoprotein VI in human platelets. European journal of biochemistry 55 10469124
1999 Clnk, a novel SLP-76-related adaptor molecule expressed in cytokine-stimulated hemopoietic cells. The Journal of experimental medicine 55 10562326
2002 Differential SLP-76 expression and TCR-mediated signaling in effector and memory CD4 T cells. Journal of immunology (Baltimore, Md. : 1950) 53 11823482
2000 Functional association between SLAP-130 and SLP-76 in Jurkat T cells. The Journal of biological chemistry 52 10671560
2012 Attenuation of T cell receptor signaling by serine phosphorylation-mediated lysine 30 ubiquitination of SLP-76 protein. The Journal of biological chemistry 50 22902619
2006 Functional hierarchy of the N-terminal tyrosines of SLP-76. Journal of immunology (Baltimore, Md. : 1950) 49 16456002
2001 Mechanisms of signaling by the hematopoietic-specific adaptor proteins, SLP-76 and LAT and their B cell counterpart, BLNK/SLP-65. Advances in immunology 48 11680012
2006 Dual role of SLP-76 in mediating T cell receptor-induced activation of phospholipase C-gamma1. The Journal of biological chemistry 45 17148460
2000 Resting lymphocyte kinase (Rlk/Txk) targets lymphoid adaptor SLP-76 in the cooperative activation of interleukin-2 transcription in T-cells. The Journal of biological chemistry 44 10660534
2000 Adapter proteins SLP-76 and BLNK both are expressed by murine macrophages and are linked to signaling via Fcgamma receptors I and II/III. Proceedings of the National Academy of Sciences of the United States of America 44 10677525
1999 SLP-76 binding to p56lck: a role for SLP-76 in CD4-induced desensitization of the TCR/CD3 signaling complex. Journal of immunology (Baltimore, Md. : 1950) 44 10477581
2005 Conditional deletion reveals a cell-autonomous requirement of SLP-76 for thymocyte selection. The Journal of experimental medicine 42 16186188
2001 Synergistic regulation of immunoreceptor signaling by SLP-76-related adaptor Clnk and serine/threonine protein kinase HPK-1. Molecular and cellular biology 42 11509653
2013 Multipoint binding of the SLP-76 SH2 domain to ADAP is critical for oligomerization of SLP-76 signaling complexes in stimulated T cells. Molecular and cellular biology 41 23979596
2010 Coordination of receptor signaling in multiple hematopoietic cell lineages by the adaptor protein SLP-76. Cold Spring Harbor perspectives in biology 41 20452948
2006 Disruption of SLP-76 interaction with Gads inhibits dynamic clustering of SLP-76 and FcepsilonRI signaling in mast cells. Molecular and cellular biology 41 16479002
2000 A BASH/SLP-76-related adaptor protein MIST/Clnk involved in IgE receptor-mediated mast cell degranulation. International immunology 40 10744659
2012 Studying the dynamics of SLP-76, Nck, and Vav1 multimolecular complex formation in live human cells with triple-color FRET. Science signaling 39 22534133
2021 Targeting adaptor protein SLP76 of RAGE as a therapeutic approach for lethal sepsis. Nature communications 38 33436632
2007 Efficient T-cell receptor signaling requires a high-affinity interaction between the Gads C-SH3 domain and the SLP-76 RxxK motif. The EMBO journal 38 17235283
2000 Roles of SLP-76, phosphoinositide 3-kinase, and gelsolin in the platelet shape changes initiated by the collagen receptor GPVI/FcR gamma-chain complex. Blood 38 11090061
2011 Role of two adaptor molecules SLP-76 and LAT in the PI3K signaling pathway in activated T cells. Journal of immunology (Baltimore, Md. : 1950) 37 21282515
1999 Allelic exclusion of the T cell receptor beta locus requires the SH2 domain-containing leukocyte protein (SLP)-76 adaptor protein. The Journal of experimental medicine 37 10523607
1999 NK cytokine secretion and cytotoxicity occur independently of the SLP-76 adaptor protein. European journal of immunology 36 10427985
1996 Hematopoietic cell phosphatase, SHP-1, is constitutively associated with the SH2 domain-containing leukocyte protein, SLP-76, in B cells. The Journal of experimental medicine 36 8760799
2007 Mitogenic CD28 signals require the exchange factor Vav1 to enhance TCR signaling at the SLP-76-Vav-Itk signalosome. Journal of immunology (Baltimore, Md. : 1950) 35 17237383
2007 Prevalence of ZAP-70, LAT, SLP-76, and DNA methyltransferase 1 expression in CD4+ T cells of patients with systemic lupus erythematosus. Clinical rheumatology 35 17492476
2005 Membrane localization and function of Vav3 in T cells depend on its association with the adapter SLP-76. The Journal of biological chemistry 35 15708849
2003 Independent CD28 signaling via VAV and SLP-76: a model for in trans costimulation. Immunological reviews 34 12670393