TCR Signaling

The T-Cell Receptor is a protein complex on the surface of T-cell responsible for antigen recognition. The activation induces a number of signaling cascades finally leading to the transcription of several gene products which allow the T cells to differentiate, proliferate and secrete a number of cytokines.

Src-family kinases (SFKs1 ) Lck and Fyn phosphorylate TCR ITAMs (immunoreceptor tyrosine-based activation motifs) in the CD3, creating a docking site for ZAP-70. Phosphorylation and activation is modulated by CD45 receptor2 . Zap-70 binds to CD3 zeta chain which positions the protein kinase to phosphorylate the transmembrane protein linker of activated T cells (LAT).

Signaling proteins like SLP-76 can now dock to LAT and gets phosporylated by ZAP-70 as well3. SLP-76 promotes recruitment of Vav (GEF), the adaptor proteins NCK and GADS, and an inducible T cell kinase (Itk). Ltk enables PLCγ1 by phosphorylation which leads to hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) to produce the second messengers diacylglycerol (DAG) and inositol trisphosphate (IP3).

Phosphorylation of phospholipase C γ1 (PLCγ1) by Itk results in the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) to produce the second messenger inositol trisphosphate (IP3) and DAG. DAG activates PKC4 and the MAPK/Erk pathways cascade which leads to activation of transcription factor NF-κB and ATF2 activation and relocation into nucleolus. IP3 promotes release of Ca2+ from the ER, which triggers entry of extracellular Ca2+ into cells through calcium release-activated Ca2+ (CRAC) channels. Calcium-bound calmodulin (Ca2+/CaM) activates the phosphatase calcineurin. Transcription factor NFAT gets activated and promotes IL-2 gene transcription.

The signal cascades are regulated on several occasions to diversify the cell answer. Extracellular signals are recognized by additional cell surface receptors like CD28 or LFA-1 and further regulate cellular response.


References:

  1. Braiman, A and Isakov, N (2015): "The Role of Crk Adaptor Proteins in T-Cell Adhesion and Migration”. Front. Immunol., v.6,2015. [PMID: 4593252]
  2. Courtney, AH (2017): “A Phosphosite within the SH2 Domain of Lck Regulates Its Activation by CD45. ”. Mol Cell , 3;67(3):498-511 [PMID: 28735895]
  3. Wang HY (2001): “Cbl promotes ubiquitination of the T cell receptor zeta through an adaptor function of Zap-70.” J Biol Chem, 276(28):26004-11. [PMID: 11353765]
  4. Lio Y (1999): “Protein kinase C activation inhibits tyrosine phosphorylation of Cbl and its recruitment of Src homology 2 domain-containing proteins.” J Immunol, 162(12):7095-101 [PMID: 10358153]


Receptor and Membrane Proteins

CD28 (CD28):

The protein encoded by this gene is essential for T-cell proliferation and survival, cytokine production, and T-helper type-2 development. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2011].   更多...

CD4 (CD4 Molecule):

TRAT1 - T Cell Receptor Associated Transmembrane Adaptor 1

此分类里的别的抗原:
B2M - beta-2 Microglobulin: B2M 抗体 B2M ELISA试剂盒 B2M 蛋白
CD247 (CD247 Molecule): CD247 抗体 CD247 ELISA试剂盒 CD247 蛋白
CD3E (CD3e Molecule, epsilon (CD3-TCR Complex)): CD3E 抗体 CD3E ELISA试剂盒 CD3E 蛋白
CD3G (CD3g Molecule, gamma (CD3-TCR Complex)): CD3G 抗体 CD3G ELISA试剂盒 CD3G 蛋白
CD3D (CD3d Molecule, delta (CD3-TCR Complex)): CD3D 抗体 CD3D ELISA试剂盒 CD3D 蛋白
CD8A (CD8 Antigen, alpha Polypeptide): CD8A 抗体    
CD80 (CD80): CD80 抗体 CD80 ELISA试剂盒 CD80 蛋白
CD86 (CD86 Molecule): CD86 抗体 CD86 ELISA试剂盒 CD86 蛋白
CD8A - CD8: CD8A 抗体 CD8A ELISA试剂盒 CD8A 蛋白
CD8B (CD8b Molecule): CD8B 抗体 CD8B ELISA试剂盒 CD8B 蛋白
HLA-DRA - HLA Class II DR alpha: HLA-DRA 抗体 HLA-DRA ELISA试剂盒 HLA-DRA 蛋白
HLA-DRB1 (HLA Class II DR beta 1): HLA-DRB1 抗体 HLA-DRB1 ELISA试剂盒 HLA-DRB1 蛋白
HLA-DRB3 (HLA Class II DR beta 3): HLA-DRB3 抗体   HLA-DRB3 蛋白
HLADRB4 - HLA Class II DR beta 4: HLADRB4 抗体   HLADRB4 蛋白
HLA-ABC - HLA-ABC: HLA-ABC 抗体    
LAT (Linker For Activation of T Cells): LAT 抗体 LAT ELISA试剂盒 LAT 蛋白
HLA-A (Major Histocompatibility Complex, Class I, A): HLA-A 抗体 HLA-A ELISA试剂盒 HLA-A 蛋白
HLA-DPA1 - Major Histocompatibility Complex, Class II, DP alpha 1: HLA-DPA1 抗体 HLA-DPA1 ELISA试剂盒 HLA-DPA1 蛋白
HLA-DPB1 (Major Histocompatibility Complex, Class II, DP beta 1): HLA-DPB1 抗体   HLA-DPB1 蛋白
HLADQA1 - Major Histocompatibility Complex, Class II, DQ alpha 1: HLADQA1 抗体 HLADQA1 ELISA试剂盒 HLADQA1 蛋白
HLA-DQA2 - Major Histocompatibility Complex, Class II, DQ alpha 2: HLA-DQA2 抗体   HLA-DQA2 蛋白
HLA-DQB1 (Major Histocompatibility Complex, Class II, DQ beta 1): HLA-DQB1 抗体 HLA-DQB1 ELISA试剂盒 HLA-DQB1 蛋白
HLA-DQB2 (Major Histocompatibility Complex, Class II, DQ beta 2): HLA-DQB2 抗体   HLA-DQB2 蛋白
HLA-DRB5 (Major Histocompatibility Complex, Class II, DR beta 5): HLA-DRB5 抗体 HLA-DRB5 ELISA试剂盒 HLA-DRB5 蛋白
SHC1 (SHC (Src Homology 2 Domain Containing) Transforming Protein 1): SHC1 抗体 SHC1 ELISA试剂盒 SHC1 蛋白
SLC25A20 - Solute Carrier Family 25 (Carnitine/acylcarnitine Translocase), Member 20: SLC25A20 抗体 SLC25A20 ELISA试剂盒 SLC25A20 蛋白
TRAF6 (TNF Receptor-Associated Factor 6): TRAF6 抗体 TRAF6 ELISA试剂盒 TRAF6 蛋白
TMEM189 (Transmembrane Protein 189): TMEM189 抗体 TMEM189 ELISA试剂盒 TMEM189 蛋白

Adaptor Proteins and Regulators

此分类里的别的抗原:
GAB2 (GRB2-Associated Binding Protein 2): GAB2 抗体 GAB2 ELISA试剂盒 GAB2 蛋白
GRAP2 (GRB2-Related Adaptor Protein 2): GRAP2 抗体 GRAP2 ELISA试剂盒 GRAP2 蛋白
GRB2 (Growth Factor Receptor-Bound Protein 2): GRB2 抗体 GRB2 ELISA试剂盒 GRB2 蛋白
LCP2 (Lymphocyte Cytosolic Protein 2 (SH2 Domain Containing Leukocyte Protein of 76kDa)): LCP2 抗体 LCP2 ELISA试剂盒 LCP2 蛋白
MALT1 (Mucosa Associated Lymphoid Tissue Lymphoma Translocation Gene 1): MALT1 抗体 MALT1 ELISA试剂盒 MALT1 蛋白
NCK1 - Cytoplasmic Protein NCK1: NCK1 抗体 NCK1 ELISA试剂盒 NCK1 蛋白
PAG1 (phosphoprotein Associated with Glycosphingolipid Microdomains 1): PAG1 抗体 PAG1 ELISA试剂盒 PAG1 蛋白
PTPN11 (Protein tyrosine Phosphatase, Non-Receptor Type 11): PTPN11 抗体 PTPN11 ELISA试剂盒 PTPN11 蛋白
PTPRC - CD45: PTPRC 抗体 PTPRC ELISA试剂盒 PTPRC 蛋白
PTPN6 (Protein-tyrosine Phosphatase 1C): PTPN6 抗体 PTPN6 ELISA试剂盒 PTPN6 蛋白
SH3BP2 - SH3-Domain Binding Protein 2: SH3BP2 抗体 SH3BP2 ELISA试剂盒 SH3BP2 蛋白

GEFs and PLCs (Ca2+ regulated)

此分类里的别的抗原:
CBL (Cas-Br-M (Murine) Ecotropic Retroviral Transforming Sequence): CBL 抗体 CBL ELISA试剂盒 CBL 蛋白
CDC42 (Cell Division Cycle 42): CDC42 抗体 CDC42 ELISA试剂盒  
CDC42 (Cell Division Cycle 42 (GTP Binding Protein, 25kDa)): CDC42 抗体 CDC42 ELISA试剂盒 CDC42 蛋白
FLNA - Filamin A: FLNA 抗体 FLNA ELISA试剂盒 FLNA 蛋白
ORAI1 (ORAI Calcium Release-Activated Calcium Modulator 1): ORAI1 抗体 ORAI1 ELISA试剂盒  
PTEN (Phosphatase and Tensin Homolog): PTEN 抗体    
PIPLC - Phosphoinositide-Specific phospholipase C:   PIPLC ELISA试剂盒  
PLC (Phospholipase C): PLC 抗体 PLC ELISA试剂盒 PLC 蛋白
PLC1 - Phospholipase C 1: PLC1 抗体    
PLCG1 - Phospholipase C gamma 1: PLCG1 抗体 PLCG1 ELISA试剂盒 PLCG1 蛋白
RAP1A (RAP1A, Member of RAS Oncogene Family): RAP1A 抗体 RAP1A ELISA试剂盒 RAP1A 蛋白
RASSF5 (Ras Association (RalGDS/AF-6) Domain Family Member 5): RASSF5 抗体 RASSF5 ELISA试剂盒 RASSF5 蛋白
RASGRP1 - RAS Guanyl Releasing Protein 1 (Calcium and DAG-Regulated): RASGRP1 抗体 RASGRP1 ELISA试剂盒 RASGRP1 蛋白
RASGRP2 (RAS Guanyl Releasing Protein 2 (Calcium and DAG-Regulated)): RASGRP2 抗体 RASGRP2 ELISA试剂盒 RASGRP2 蛋白
SOS1 (Son of Sevenless Homolog 1 (Drosophila)): SOS1 抗体 SOS1 ELISA试剂盒 SOS1 蛋白
STIM1 (Stromal Interaction Molecule 1): STIM1 抗体 STIM1 ELISA试剂盒 STIM1 蛋白
TRPV6 (Transient Receptor Potential Cation Channel, Subfamily V, Member 6): TRPV6 抗体 TRPV6 ELISA试剂盒 TRPV6 蛋白
VASP (Vasodilator-Stimulated phosphoprotein): VASP 抗体 VASP ELISA试剂盒 VASP 蛋白
VAV1 (Vav 1 Oncogene): VAV1 抗体 VAV1 ELISA试剂盒 VAV1 蛋白

Kinases

ZAP70 (zeta-Chain (TCR) Associated Protein Kinase 70kDa):

此分类里的别的抗原:
PDPK1 (3-phosphoinositide Dependent Protein Kinase-1): PDPK1 抗体 PDPK1 ELISA试剂盒 PDPK1 蛋白
AURKB - Aurora Kinase B: AURKB 抗体 AURKB ELISA试剂盒 AURKB 蛋白
CSK (C-Src tyrosine Kinase): CSK 抗体 CSK ELISA试剂盒 CSK 蛋白
CHUK (conserved Helix-Loop-Helix Ubiquitous Kinase): CHUK 抗体 CHUK ELISA试剂盒 CHUK 蛋白
DRB1 - Dopamine Receptor Binding 1: DRB1 抗体    
DBNL (Drebrin-Like): DBNL 抗体 DBNL ELISA试剂盒 DBNL 蛋白
FYN (FYN Oncogene Related To SRC, FGR, YES): FYN 抗体 FYN ELISA试剂盒 FYN 蛋白
FYB (FYN-Binding Protein): FYB 抗体 FYB ELISA试剂盒 FYB 蛋白
ITK (IL2-Inducible T-Cell Kinase): ITK 抗体 ITK ELISA试剂盒 ITK 蛋白
INPP5D - Inositol Polyphosphate-5-Phosphatase, 145kDa: INPP5D 抗体 INPP5D ELISA试剂盒 INPP5D 蛋白
LCK (Lymphocyte-Specific Protein tyrosine Kinase): LCK 抗体 LCK ELISA试剂盒 LCK 蛋白
MAP3K14 (Mitogen-Activated Protein Kinase Kinase Kinase 14): MAP3K14 抗体 MAP3K14 ELISA试剂盒 MAP3K14 蛋白
MAP3K7 (Mitogen-Activated Protein Kinase Kinase Kinase 7): MAP3K7 抗体 MAP3K7 ELISA试剂盒 MAP3K7 蛋白
MAP3K8 (Mitogen-Activated Protein Kinase Kinase Kinase 8): MAP3K8 抗体 MAP3K8 ELISA试剂盒 MAP3K8 蛋白
MAP4K1 (Mitogen-Activated Protein Kinase Kinase Kinase Kinase 1): MAP4K1 抗体   MAP4K1 蛋白
PAK1 (P21-Activated Kinase 1): PAK1 抗体 PAK1 ELISA试剂盒 PAK1 蛋白
PAK2 (P21-Activated Kinase 2): PAK2 抗体 PAK2 ELISA试剂盒 PAK2 蛋白
PIK3CA (Phosphoinositide-3-Kinase, Catalytic, alpha Polypeptide): PIK3CA 抗体 PIK3CA ELISA试剂盒 PIK3CA 蛋白
PI3K - Phosphotylinosital 3 Kinase: PI3K 抗体 PI3K ELISA试剂盒 PI3K 蛋白
PKC - Protein Kinase C: PKC 抗体 PKC ELISA试剂盒  
PKCa - PKC alpha: PKCa 抗体 PKCa ELISA试剂盒 PKCa 蛋白
PRKCB - PKC beta: PRKCB 抗体 PRKCB ELISA试剂盒 PRKCB 蛋白
PRKCE (Protein Kinase C, epsilon): PRKCE 抗体 PRKCE ELISA试剂盒 PRKCE 蛋白
PRKCQ - PKC theta: PRKCQ 抗体 PRKCQ ELISA试剂盒 PRKCQ 蛋白
RIPK2 (Receptor-Interacting Serine-threonine Kinase 2): RIPK2 抗体 RIPK2 ELISA试剂盒 RIPK2 蛋白
TAB2 (TGF-beta Activated Kinase 1/MAP3K7 Binding Protein 2): TAB2 抗体 TAB2 ELISA试剂盒 TAB2 蛋白
AKT1 - AKT: AKT1 抗体 AKT1 ELISA试剂盒 AKT1 蛋白

Transcription Factors

此分类里的别的抗原:
BCL10 (B-Cell CLL/lymphoma 10): BCL10 抗体 BCL10 ELISA试剂盒 BCL10 蛋白
CARD11 (Caspase Recruitment Domain Family, Member 11): CARD11 抗体 CARD11 ELISA试剂盒 CARD11 蛋白
CCK - Cholecystokinin: CCK 抗体 CCK ELISA试剂盒 CCK 蛋白
CREBBP - CBP: CREBBP 抗体 CREBBP ELISA试剂盒 CREBBP 蛋白
IKBKB (Inhibitor of kappa Light Polypeptide Gene Enhancer in B-Cells, Kinase beta): IKBKB 抗体 IKBKB ELISA试剂盒 IKBKB 蛋白
IKBKG (Inhibitor of kappa Light Polypeptide Gene Enhancer in B-Cells, Kinase gamma): IKBKG 抗体 IKBKG ELISA试剂盒 IKBKG 蛋白
NFKB1 (Nuclear Factor of kappa Light Polypeptide Gene Enhancer in B-Cells 1): NFKB1 抗体 NFKB1 ELISA试剂盒 NFKB1 蛋白
NFKBIA (Nuclear Factor of kappa Light Polypeptide Gene Enhancer in B-Cells Inhibitor, alpha): NFKBIA 抗体 NFKBIA ELISA试剂盒 NFKBIA 蛋白
NFkBP65 - p65: NFkBP65 抗体 NFkBP65 ELISA试剂盒 NFkBP65 蛋白
NR2C2 - Nuclear Receptor Subfamily 2, Group C, Member 2: NR2C2 抗体 NR2C2 ELISA试剂盒 NR2C2 蛋白
RIP2 (ROP Interactive Partner 2): RIP2 抗体    
UBE2V1 (Ubiquitin-Conjugating Enzyme E2 Variant 1): UBE2V1 抗体 UBE2V1 ELISA试剂盒 UBE2V1 蛋白
UBE2N (Ubiquitin-Conjugating Enzyme E2N): UBE2N 抗体 UBE2N ELISA试剂盒 UBE2N 蛋白