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:
- 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]
- 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]
- 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]
- 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):
This gene encodes a gamma-aminobutyric acid (GABA) receptor. GABA is the major inhibitory neurotransmitter in the mammlian brain, where it acts at GABA-A receptors, which are ligand-gated chloride channels. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. Mutations in this gene have been associated with epilepsy and febrile...
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CD4 (CD4 Molecule):
This gene encodes a membrane glycoprotein of T lymphocytes that interacts with major histocompatibility complex class II antigenes and is also a...
TRAT1 - T Cell Receptor Associated Transmembrane Adaptor 1
Stabilizes the TCR (T-cell antigen receptor)/CD3 complex at the surface of T-cells (By similarity).
| 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): | |||
| 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 蛋白 | |
| HLA-DQA2 - Major Histocompatibility Complex, Class II, DQ alpha 2: | HLA-DQA2 抗体 | ||
| 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 蛋白 | |
Adaptor Proteins and Regulators
| 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 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)
| 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): | |||
| 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 蛋白 | |
| RASGRP1 - RAS Guanyl Releasing Protein 1 (Calcium and DAG-Regulated): | RASGRP1 抗体 | RASGRP1 蛋白 | |
| RASGRP2 (RAS Guanyl Releasing Protein 2 (Calcium and DAG-Regulated)): | RASGRP2 抗体 | RASGRP2 蛋白 | |
| SOS1 (Son of Sevenless Homolog 1 (Drosophila)): | SOS1 抗体 | 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 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):
This gene encodes an enzyme belonging to the protein tyrosine kinase family, and it plays a role in T-cell development and lymphocyte activation....
| 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 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 ELISA试剂盒 | 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
| 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 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 蛋白 |
