LAT (Ab-255) Antibody

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Cat. No.
BT1799480
Synonyms
LAT; Linker for activation of T-cells family member 1; 36 kDa phospho-tyrosine adapter protein; pp36; p36-38
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Description

Definition and Target Specificity

LAT (Ab-255) Antibody is a polyclonal antibody raised in rabbits against a synthesized non-phosphopeptide derived from the human LAT protein around the phosphorylation site of Tyr255 . LAT is a transmembrane adaptor protein essential for coupling T-cell receptor (TCR) and pre-TCR signaling to downstream events, including calcium mobilization, MAPK activation, and cytoskeletal reorganization .

Key target features:

  • Epitope: Tyrosine 255 (Tyr255) phosphorylation site

  • Protein role: Facilitates signal transduction in TCR, FcγR (NK cells), and FcεR (mast cells)

  • Molecular weight: ~36–38 kDa (unphosphorylated LAT migrates faster than phosphorylated forms)

Signaling Pathway Analysis

  • T-cell activation: LAT phosphorylation at Tyr255 is critical for recruiting PLCγ1, GRB2, and other signaling molecules to the TCR complex .

  • NK-cell ITAM signaling: Studies using LAT (Ab-255) revealed LAT phosphorylation during DAP12-coupled receptor activation (e.g., Ly49D), linking ITAM motifs to downstream Syk/ZAP70 kinases .

Disease Mechanisms

  • Immune dysregulation: Mice lacking LAT exhibit skewed Ly49 receptor repertoires and impaired NK1.1 responses, highlighting LAT’s role in fine-tuning NK-cell activity .

  • Therapeutic targeting: LAT’s involvement in FcεR-mediated mast cell activation positions it as a candidate for allergy and asthma research .

Functional Insights

  • Dual adaptor interplay: In NK cells, LAT and LAB (LAT2) redundantly regulate ITAM signaling. Activated NK cells shift dependency to LAT upon interleukin-2 stimulation, suppressing Syk pathways .

  • Phosphorylation kinetics: Crosslinking Ly49D or CD16 in human NK cells induces rapid LAT phosphorylation (peaking at 1 minute), demonstrating its direct role in DAP12 signaling .

Limitations and Considerations

  • Specificity: Cross-reactivity with homologous phosphorylation sites in related proteins requires validation via knockout controls .

  • Storage stability: Sodium azide preservative mandates careful handling .

Product Specs

Form
Rabbit IgG in phosphate buffered saline (without Mg2+ and Ca2+), pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol.
Lead Time
Typically, we can ship products within 1-3 business days of receiving your order. Delivery time may vary depending on the purchasing method or location. Please consult your local distributor for specific delivery details.
Synonyms
LAT; Linker for activation of T-cells family member 1; 36 kDa phospho-tyrosine adapter protein; pp36; p36-38
Target Names
LAT
Uniprot No.
O43561

Target Background

Function
LAT (Linker for Activation of T cells) is a crucial adaptor protein involved in T-cell receptor (TCR) and pre-TCR-mediated signaling pathways, playing a vital role in both mature T-cell function and T-cell development. Its role extends beyond T cells, as it is also implicated in FCGR3 (low affinity immunoglobulin gamma Fc region receptor III)-mediated signaling in natural killer cells and FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. LAT acts as a crucial intermediary, coupling activation of these receptors and their associated kinases to downstream intracellular events. These events include the mobilization of intracellular calcium stores, PKC activation, MAPK activation, and cytoskeletal reorganization. This intricate process is mediated through the recruitment of key signaling molecules like PLCG1, GRB2, and GRAP2.
Gene References Into Functions
  1. Plasma membrane LAT activation precedes vesicular recruitment, defining two distinct phases in early T-cell activation. PMID: 29789604
  2. Overexpression of LAT1 is associated with unfavorable prognosis, linked to tumor grade, proliferative potential, and angiogenesis. Furthermore, it mediates intracellular transport of anticancer agents. PMID: 28815339
  3. The cooperative binding of the growth factor receptor-bound protein 2 family to LAT, driven by dimerization, potentially enhances antigen receptor sensitivity. This mechanism is achieved by reducing signalosome formation at incompletely phosphorylated LAT molecules, prioritizing the formation of complete signalosomes. PMID: 28951535
  4. Nur77 exhibits a suppressive effect on CD4(+) T cell proliferation and reveals a regulatory role for Irf4 in TH2 polarization. Reducing Irf4 gene dosage leads to an increase in GATA3(+) and IL-4(+) cells. PMID: 28538176
  5. Dephosphorylation of LAT and phospholipase C-gamma by SHP-1 inhibits natural killer cell cytotoxicity. PMID: 27221712
  6. A study delved into molecular mobility within LAT:Grb2:SOS assemblies on supported membranes using single-molecule tracking. Trajectory analysis revealed a characteristic transition to subdiffusive motion, suggesting a loosely entangled polymer structure for the LAT:Grb2:SOS assembly. PMID: 29045874
  7. Phosphotyrosine-mediated assembly of adaptor protein LAT networks produces two distinct kinetic species of the Ras activator SOS. PMID: 27370798
  8. LAT overexpression has been linked to microcephaly. PMID: 28965845
  9. LAT and SLP-76 are randomly distributed throughout the clusters that form upon T cell receptor engagement. PMID: 27875277
  10. This research highlights the importance of considering inherited LAT deficiency in patients presenting with combined immunodeficiency characterized by T-cell abnormalities. PMID: 27522155
  11. This report describes the first instance of a LAT-related disease in humans, manifested by a progressive combined immune deficiency accompanied by severe autoimmune disease. PMID: 27242165
  12. Findings indicate that LAT1 plays a crucial role in regulating the uptake of essential amino acids, such as leucine, into endometrial cancer cells. The superior efficacy of BCH compared to LAT1 shRNA in inhibiting Ishikawa spheroid area suggests potential contributions from other LAT family members to cell growth. PMID: 27486861
  13. Evidence suggests that the T cell-specific adaptor protein (TSAd) SH2 domain interacts with CD6 antigen and LAT phosphotyrosine (pTyr) peptides. PMID: 27896837
  14. Elevated expression of LAT1 and ASCT2 is correlated with metastasis and invasion in esophageal squamous cell carcinoma. PMID: 26936531
  15. IFT20 is essential for the delivery of the intracellular pool of LAT to the immune synapse in naive primary T lymphocytes. PMID: 26715756
  16. Research indicates that palmitoylation mutation of LAT attenuates the signal transduction induced by glycosylphosphatidylinositol-anchored CD59 antigen in T cells. PMID: 26271970
  17. HSV-1-encoded Us3 protein disrupts TCR signaling and interleukin-2 production by inactivating the linker for activation of T cells. PMID: 25907557
  18. Patients with severe aplastic anemia exhibit increased LAT levels and a disrupted Th1-Th2 balance. PMID: 24673455
  19. LAT acts as a modulator of CD3zeta and ZAP-70 tyrosine phosphorylation. PMID: 24204825
  20. Mutation of the palmitoylation site of LAT-EGFP attenuates the signal transduction of CD59 in T cells. PMID: 24200054
  21. Findings demonstrate that L-type amino acid transporter 1 is a primary transporter for essential amino acids into activated human T cells. PMID: 24038088
  22. Histone hypoacetylation on the LAT promoter inhibits LAT expression and promotes Th2 differentiation. Conversely, trichostatin A, a histone deacetylase inhibitor, enhances LAT expression and suppresses Th2 cytokine production. PMID: 23360572
  23. LAT is essential for maintaining calcium homeostasis in T cells. PMID: 22998346
  24. A novel function and mechanism of TRAF6 action in the T cell receptor(TCR)-LAT signaling pathway highlights that LAT also acts as an adapter molecule in TCR/CD28-induced activation of TRAF6. PMID: 23514740
  25. LAT located at the cell surface can be rapidly recruited to activation-induced microclusters within seconds of T cell receptor (TCR) engagement. PMID: 23487428
  26. LAT cleavage may serve as a regulator of TCR-mediated T-cell activation, not solely as a transducer of cell death-promoting stimuli. PMID: 23240581
  27. Expression of a constitutively active Raf transgene enhances lymphoproliferation, suggesting a role for the Ras-MAPK pathway in LAT-mediated autoimmune hyperproliferation. PMID: 22984075
  28. Nef utilizes a dual mechanism to disrupt early TCR signaling by restricting communication between LAT and SLP-76. PMID: 22802418
  29. Modeling and simulation of LAT aggregation with molecular variability in the number of binding sites for cytosolic Grb2-SOS1-Grb2 have been performed. PMID: 22396725
  30. The segment encompassing residues 112-126 of human LAT is essential for its interaction with Lck. PMID: 22034845
  31. Activation of T cell antigen receptors leads to the recruitment and phosphorylation of LAT from subsynaptic vesicles. Studies using LAT mutants confirmed that recruitment precedes LAT phosphorylation. PMID: 21642986
  32. Evidence suggests that MAL regulates membrane order and the distribution of microtubule and transport vesicle docking machinery at the IS. Through this mechanism, MAL ensures proper protein sorting of Lck and LAT to the cSMAC. PMID: 21508261
  33. PECAM-1-mediated inhibition of GPVI-dependent platelet responses arises from the recruitment of SHP-2-p85 complexes to tyrosine-phosphorylated PECAM-1. This event diminishes the association of PI3K with activatory signaling molecules Gab1 and LAT. PMID: 20723025
  34. LAT recruits Src homology 2 domain-containing leukocyte protein of 76 kDa (SLP-76) following T-cell receptor ligation and Akt kinase phosphorylation in Jurkat cells, activating the phosphoinositide 3-hydroxykinase (PI3K) signaling cascade. PMID: 21282515
  35. Elevated expression of LAT1 is associated with squamous cell carcinoma of the lung. PMID: 19068093
  36. Research demonstrates that LAT promotes TCR signal initiation and suggests that this adaptor may contribute to the maintenance of active Lck in close proximity to its substrates. PMID: 21152094
  37. LAT ubiquitylation serves as a molecular checkpoint for the attenuation of T-cell signaling. PMID: 21282648
  38. These findings reveal a novel role for HSP90 as a positive regulator of LAT gene expression in activated T cells. PMID: 21251717
  39. The adaptor protein LAT contains several conserved serine-based motifs, crucial for proper signal transduction through the TCR. PMID: 20940326
  40. Studies indicate that LAT resides in membrane rafts and participates in signaling pathways mediated by multiple receptors beyond the T cell receptor. PMID: 20875087
  41. A significant decrease in LAT gene mRNA expression in T cells of asthmatic patients may be attributed to the upregulation of its upstream regulatory factors, Lck and ZAP-70. PMID: 18683785
  42. LAT displacement from lipid rafts constitutes a molecular mechanism by which polyunsaturated fatty acids (PUFAs) inhibit T cell signaling. PMID: 12029091
  43. Phosphorylation of LAT by Itk promotes the recruitment of Vav. PMID: 12186560
  44. LAT plays a role in T cell activation signal transduction and is stably associated with plasma membrane rafts. PMID: 12515827
  45. Interaction with the open-active form of Lck in lipid rafts reveals a novel mechanism for regulating Lck in T cells. PMID: 12570875
  46. This research examines synergistic assembly in T cell plasma membrane domains. PMID: 12646565
  47. The T cell adapter molecule LAT is required for the correct orientation of the microtubule-organizing center as it moves towards the interface between the T cell and antigen-presenting cell. PMID: 12847255
  48. This research elucidates the basis for the preferential recognition of specific LAT sites by Gads. PMID: 15029250
  49. CD3/T cell receptor complex signaling to beta 1 integrins is impaired in LAT-deficient Jurkat T cells and can be restored by expressing wild-type LAT. PMID: 15100278
  50. LAB resembles a LAT molecule incapable of binding phospholipase C-gamma1. PMID: 15153499
Database Links

HGNC: 18874

OMIM: 602354

KEGG: hsa:27040

UniGene: Hs.632179

Involvement In Disease
Immunodeficiency 52 (IMD52)
Subcellular Location
Cell membrane; Single-pass type III membrane protein. Note=Present in lipid rafts.
Tissue Specificity
Expressed in thymus, T-cells, NK cells, mast cells and, at lower levels, in spleen. Present in T-cells but not B-cells (at protein level).

Q&A

FAQs for LAT (Ab-255) Antibody in Academic Research

Advanced Research Questions

  • How to resolve contradictory data on LAT’s role in NK-cell signaling?

    • Context: LAT−/− NK cells show intact resting responses but reduced activation .

    • Analysis framework:

      • Compare resting vs. IL-2-activated NK cells:

        • Resting cells: LAB compensates for LAT .

        • Activated cells: LAT becomes critical due to Syk suppression .

      • Use Lat/Lab double-KO models to isolate pathway dependencies .

    • Key findings:

      ConditionIFNγ Production (vs. WT)
      Resting Lat−/−Normal
      Activated Lat−/−Reduced by 40–60%
      Lat/Lab−/−Nearly abolished

  • What mechanistic insights can be gained using LAT (Ab-255) in phospho-proteomic studies?

    • Approach:

      • Stimulate cells with anti-CD3/CD28 (T-cells) or anti-Ly49D (NK cells) .

      • Perform time-course WB to track Tyr255 phosphorylation (peaks at 1–2 min post-stimulation) .

      • Combine with Grb2 pulldowns to identify LAT interactors (e.g., PLCγ1, SLP-76) .

    • Critical controls:

      • Include pervanadate-treated samples to maximize phosphorylation .

      • Validate with phospho-specific antibodies (e.g., anti-pTyr191 LAT) .

  • How to design experiments studying LAT’s cross-talk with LAB in immune regulation?

    • Experimental workflow:

      1. Compare LAT (Ab-255) signal intensity in Lab−/− vs. WT NK cells .

      2. Assess LAT/LAB co-localization via immunofluorescence in lipid raft fractions .

      3. Measure downstream outputs (e.g., calcium flux, MAPK activation) in dual-KO models .

    • Data interpretation:

      • LAB hyperactivation in Lat−/− cells explains skewed Ly49 receptor profiles .

      • LAT dominance in activated cells correlates with Syk downregulation .

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