T-Zell Rezeptor Signalweg
Der T-Zell Rezeptor (TCR) ist ein Proteinkomplex auf der Oberfläche von T-Zellen und dient der Erkennung von Antigenen. Durch Aktivierung wird eine Signalkaskade in Gang gesetzt die in der T-Zelle Differenzierung, Vermehrung und Ausschüttung von Cytokinen induziert.
Src-family Kinasen (SFKs1) Lck und Fyn phosphorylieren TCR ITAMs (immunoreceptor tyrosine-based activation motifs) im CD3 Komplex und ermöglichen Zap-70 so and ITAM zu binden. Phosphorylierung und Aktivierung wird durch den CD45 Rezeptor reguliert.2. Die Bindung bringt Zap-70 in Position seinerseits das transmembrane Protein Linker of activated T-Cells (LAT) zu phosphorylisieren.
SLP-76 und andere Signalproteine binden nun an LAT und werden ebenfalls durch ZAP-70 phosphoryliert4. SLP-76 begünstigt die Bindung von Vav(GEF), den Adaptorproteinen NCK und GADS und der T-Zellkinase (Itk). Itk aktiviert PLCγ1 was zur Hydrolyse von Phosphatidylinositol 4,5-bisphosphate (PIP2) führt, die beiden sekundären Messenger Diacylglycerol (DAG) und Inositol Trisphosphate (IP3) werden gebildet. DAG aktiviert PKC4 und den MAPK/Erk Signalweg wodurch die Transkriptionsfaktoren NF-κB und ATF2 aktiviert werden. IP3 induziert die Freisetzung von Ca2+ aus dem ER, was gleichzeitig die Aufnahme von extrazellulären Ca2+ Kationen mittels Calcium Release-activated Ca2+ (CRAC) Kanälen auslöst. Calmodulin-Kalzium Komplexe aktivieren die Phosphatase Calcineurin. Transkriptionsfaktor NFAT wird ebenfalls aktiviert und ermöglicht die Transkription von IL-2 im Zellkern.
Zur Verbesserung einer zielgerichteten Zellantwort werden die Signalkaskaden an mehreren Stellen reguliert. Extrazelluläre Signale nehmen durch Oberflächenrezeptoren wie CD28 oder LFA-1 zusätzlich Einfluss.
Literatur:
- 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 Antikörper | B2M ELISA Kits | B2M Proteine |
| CD247 (CD247 Molecule): | CD247 Antikörper | CD247 ELISA Kits | CD247 Proteine |
| CD3E (CD3e Molecule, epsilon (CD3-TCR Complex)): | CD3E Antikörper | CD3E ELISA Kits | CD3E Proteine |
| CD3G (CD3g Molecule, gamma (CD3-TCR Complex)): | CD3G Antikörper | CD3G ELISA Kits | CD3G Proteine |
| CD3D (CD3d Molecule, delta (CD3-TCR Complex)): | CD3D Antikörper | CD3D ELISA Kits | CD3D Proteine |
| CD8A (CD8 Antigen, alpha Polypeptide): | |||
| CD80 (CD80): | CD80 Antikörper | CD80 ELISA Kits | CD80 Proteine |
| CD86 (CD86 Molecule): | CD86 Antikörper | CD86 ELISA Kits | CD86 Proteine |
| CD8A - CD8: | CD8A Antikörper | CD8A ELISA Kits | CD8A Proteine |
| CD8B (CD8b Molecule): | CD8B Antikörper | CD8B ELISA Kits | CD8B Proteine |
| HLA-DRA - HLA Class II DR alpha: | HLA-DRA Antikörper | HLA-DRA ELISA Kits | HLA-DRA Proteine |
| HLA-DRB1 (HLA Class II DR beta 1): | HLA-DRB1 Antikörper | HLA-DRB1 ELISA Kits | HLA-DRB1 Proteine |
| HLA-DRB3 (HLA Class II DR beta 3): | HLA-DRB3 Antikörper | HLA-DRB3 Proteine | |
| HLADRB4 - HLA Class II DR beta 4: | HLADRB4 Antikörper | HLADRB4 Proteine | |
| HLA-ABC - HLA-ABC: | HLA-ABC Antikörper | ||
| LAT (Linker For Activation of T Cells): | LAT Antikörper | LAT ELISA Kits | LAT Proteine |
| HLA-A (Major Histocompatibility Complex, Class I, A): | HLA-A Antikörper | HLA-A ELISA Kits | HLA-A Proteine |
| HLA-DPA1 - Major Histocompatibility Complex, Class II, DP alpha 1: | HLA-DPA1 Antikörper | HLA-DPA1 ELISA Kits | HLA-DPA1 Proteine |
| HLA-DPB1 (Major Histocompatibility Complex, Class II, DP beta 1): | HLA-DPB1 Antikörper | HLA-DPB1 Proteine | |
| HLADQA1 - Major Histocompatibility Complex, Class II, DQ alpha 1: | HLADQA1 Antikörper | HLADQA1 Proteine | |
| HLA-DQA2 - Major Histocompatibility Complex, Class II, DQ alpha 2: | HLA-DQA2 Antikörper | ||
| HLA-DQB1 (Major Histocompatibility Complex, Class II, DQ beta 1): | HLA-DQB1 Antikörper | HLA-DQB1 ELISA Kits | HLA-DQB1 Proteine |
| HLA-DQB2 (Major Histocompatibility Complex, Class II, DQ beta 2): | HLA-DQB2 Antikörper | HLA-DQB2 Proteine | |
| HLA-DRB5 (Major Histocompatibility Complex, Class II, DR beta 5): | HLA-DRB5 Antikörper | HLA-DRB5 ELISA Kits | HLA-DRB5 Proteine |
| SHC1 (SHC (Src Homology 2 Domain Containing) Transforming Protein 1): | SHC1 Antikörper | SHC1 ELISA Kits | SHC1 Proteine |
| SLC25A20 - Solute Carrier Family 25 (Carnitine/acylcarnitine Translocase), Member 20: | SLC25A20 Antikörper | SLC25A20 ELISA Kits | SLC25A20 Proteine |
| TRAF6 (TNF Receptor-Associated Factor 6): | TRAF6 Antikörper | TRAF6 ELISA Kits | TRAF6 Proteine |
| TMEM189 (Transmembrane Protein 189): | TMEM189 Antikörper | TMEM189 Proteine | |
Adaptor Proteins and Regulators
| GAB2 (GRB2-Associated Binding Protein 2): | GAB2 Antikörper | GAB2 ELISA Kits | GAB2 Proteine |
| GRAP2 (GRB2-Related Adaptor Protein 2): | GRAP2 Antikörper | GRAP2 ELISA Kits | GRAP2 Proteine |
| GRB2 (Growth Factor Receptor-Bound Protein 2): | GRB2 Antikörper | GRB2 ELISA Kits | GRB2 Proteine |
| LCP2 (Lymphocyte Cytosolic Protein 2 (SH2 Domain Containing Leukocyte Protein of 76kDa)): | LCP2 Antikörper | LCP2 ELISA Kits | LCP2 Proteine |
| MALT1 (Mucosa Associated Lymphoid Tissue Lymphoma Translocation Gene 1): | MALT1 Antikörper | MALT1 Proteine | |
| NCK1 - Cytoplasmic Protein NCK1: | NCK1 Antikörper | NCK1 ELISA Kits | NCK1 Proteine |
| PAG1 (phosphoprotein Associated with Glycosphingolipid Microdomains 1): | PAG1 Antikörper | PAG1 ELISA Kits | PAG1 Proteine |
| PTPN11 (Protein tyrosine Phosphatase, Non-Receptor Type 11): | PTPN11 Antikörper | PTPN11 ELISA Kits | PTPN11 Proteine |
| PTPRC - CD45: | PTPRC Antikörper | PTPRC ELISA Kits | PTPRC Proteine |
| PTPN6 (Protein-tyrosine Phosphatase 1C): | PTPN6 Antikörper | PTPN6 ELISA Kits | PTPN6 Proteine |
| SH3BP2 - SH3-Domain Binding Protein 2: | SH3BP2 Antikörper | SH3BP2 ELISA Kits | SH3BP2 Proteine |
GEFs and PLCs (Ca2+ regulated)
| CBL (Cas-Br-M (Murine) Ecotropic Retroviral Transforming Sequence): | CBL Antikörper | CBL ELISA Kits | CBL Proteine |
| CDC42 (Cell Division Cycle 42): | CDC42 Antikörper | CDC42 ELISA Kits | |
| CDC42 (Cell Division Cycle 42 (GTP Binding Protein, 25kDa)): | CDC42 Antikörper | CDC42 ELISA Kits | CDC42 Proteine |
| FLNA - Filamin A: | FLNA Antikörper | FLNA ELISA Kits | FLNA Proteine |
| ORAI1 (ORAI Calcium Release-Activated Calcium Modulator 1): | ORAI1 Antikörper | ORAI1 ELISA Kits | |
| PTEN (Phosphatase and Tensin Homolog): | |||
| PIPLC - Phosphoinositide-Specific phospholipase C: | PIPLC ELISA Kits | ||
| PLC (Phospholipase C): | PLC Antikörper | PLC ELISA Kits | PLC Proteine |
| PLC1 - Phospholipase C 1: | PLC1 Antikörper | ||
| PLCG1 - Phospholipase C gamma 1: | PLCG1 Antikörper | PLCG1 ELISA Kits | PLCG1 Proteine |
| RAP1A (RAP1A, Member of RAS Oncogene Family): | RAP1A Antikörper | RAP1A ELISA Kits | RAP1A Proteine |
| RASSF5 (Ras Association (RalGDS/AF-6) Domain Family Member 5): | RASSF5 Antikörper | RASSF5 Proteine | |
| RASGRP1 - RAS Guanyl Releasing Protein 1 (Calcium and DAG-Regulated): | RASGRP1 Antikörper | RASGRP1 Proteine | |
| RASGRP2 (RAS Guanyl Releasing Protein 2 (Calcium and DAG-Regulated)): | RASGRP2 Antikörper | RASGRP2 Proteine | |
| SOS1 (Son of Sevenless Homolog 1 (Drosophila)): | SOS1 Antikörper | SOS1 Proteine | |
| STIM1 (Stromal Interaction Molecule 1): | STIM1 Antikörper | STIM1 ELISA Kits | STIM1 Proteine |
| TRPV6 (Transient Receptor Potential Cation Channel, Subfamily V, Member 6): | TRPV6 Antikörper | TRPV6 Proteine | |
| VASP (Vasodilator-Stimulated phosphoprotein): | VASP Antikörper | VASP ELISA Kits | VASP Proteine |
| VAV1 (Vav 1 Oncogene): | VAV1 Antikörper | VAV1 ELISA Kits | VAV1 Proteine |
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 Antikörper | PDPK1 ELISA Kits | PDPK1 Proteine |
| AURKB - Aurora Kinase B: | AURKB Antikörper | AURKB ELISA Kits | AURKB Proteine |
| CSK (C-Src tyrosine Kinase): | CSK Antikörper | CSK ELISA Kits | CSK Proteine |
| CHUK (conserved Helix-Loop-Helix Ubiquitous Kinase): | CHUK Antikörper | CHUK ELISA Kits | CHUK Proteine |
| DRB1 - Dopamine Receptor Binding 1: | DRB1 Antikörper | ||
| DBNL (Drebrin-Like): | DBNL Antikörper | DBNL ELISA Kits | DBNL Proteine |
| FYN (FYN Oncogene Related To SRC, FGR, YES): | FYN Antikörper | FYN ELISA Kits | FYN Proteine |
| FYB (FYN-Binding Protein): | FYB Antikörper | FYB ELISA Kits | FYB Proteine |
| ITK (IL2-Inducible T-Cell Kinase): | ITK Antikörper | ITK ELISA Kits | ITK Proteine |
| INPP5D - Inositol Polyphosphate-5-Phosphatase, 145kDa: | INPP5D Antikörper | INPP5D ELISA Kits | INPP5D Proteine |
| LCK (Lymphocyte-Specific Protein tyrosine Kinase): | LCK Antikörper | LCK ELISA Kits | LCK Proteine |
| MAP3K14 (Mitogen-Activated Protein Kinase Kinase Kinase 14): | MAP3K14 Antikörper | MAP3K14 Proteine | |
| MAP3K7 (Mitogen-Activated Protein Kinase Kinase Kinase 7): | MAP3K7 Antikörper | MAP3K7 ELISA Kits | MAP3K7 Proteine |
| MAP3K8 (Mitogen-Activated Protein Kinase Kinase Kinase 8): | MAP3K8 Antikörper | MAP3K8 ELISA Kits | MAP3K8 Proteine |
| MAP4K1 (Mitogen-Activated Protein Kinase Kinase Kinase Kinase 1): | MAP4K1 Antikörper | MAP4K1 Proteine | |
| PAK1 (P21-Activated Kinase 1): | PAK1 Antikörper | PAK1 ELISA Kits | PAK1 Proteine |
| PAK2 (P21-Activated Kinase 2): | PAK2 Antikörper | PAK2 ELISA Kits | PAK2 Proteine |
| PIK3CA (Phosphoinositide-3-Kinase, Catalytic, alpha Polypeptide): | PIK3CA Antikörper | PIK3CA ELISA Kits | PIK3CA Proteine |
| PI3K - Phosphotylinosital 3 Kinase: | PI3K Antikörper | PI3K ELISA Kits | PI3K Proteine |
| PKC - Protein Kinase C: | PKC Antikörper | PKC ELISA Kits | |
| PKCa - PKC alpha: | PKCa Antikörper | PKCa ELISA Kits | PKCa Proteine |
| PRKCB - PKC beta: | PRKCB Antikörper | PRKCB ELISA Kits | PRKCB Proteine |
| PRKCE (Protein Kinase C, epsilon): | PRKCE Antikörper | PRKCE ELISA Kits | PRKCE Proteine |
| PRKCQ - PKC theta: | PRKCQ Antikörper | PRKCQ ELISA Kits | PRKCQ Proteine |
| RIPK2 (Receptor-Interacting Serine-threonine Kinase 2): | RIPK2 Antikörper | RIPK2 ELISA Kits | RIPK2 Proteine |
| TAB2 (TGF-beta Activated Kinase 1/MAP3K7 Binding Protein 2): | TAB2 Antikörper | TAB2 ELISA Kits | TAB2 Proteine |
| AKT1 - AKT: | AKT1 Antikörper | AKT1 ELISA Kits | AKT1 Proteine |
Transcription Factors
| BCL10 (B-Cell CLL/lymphoma 10): | BCL10 Antikörper | BCL10 ELISA Kits | BCL10 Proteine |
| CARD11 (Caspase Recruitment Domain Family, Member 11): | CARD11 Antikörper | CARD11 Proteine | |
| CCK - Cholecystokinin: | CCK Antikörper | CCK ELISA Kits | CCK Proteine |
| CREBBP - CBP: | CREBBP Antikörper | CREBBP ELISA Kits | CREBBP Proteine |
| IKBKB (Inhibitor of kappa Light Polypeptide Gene Enhancer in B-Cells, Kinase beta): | IKBKB Antikörper | IKBKB ELISA Kits | IKBKB Proteine |
| IKBKG (Inhibitor of kappa Light Polypeptide Gene Enhancer in B-Cells, Kinase gamma): | IKBKG Antikörper | IKBKG ELISA Kits | IKBKG Proteine |
| NFKB1 (Nuclear Factor of kappa Light Polypeptide Gene Enhancer in B-Cells 1): | NFKB1 Antikörper | NFKB1 ELISA Kits | NFKB1 Proteine |
| NFKBIA (Nuclear Factor of kappa Light Polypeptide Gene Enhancer in B-Cells Inhibitor, alpha): | NFKBIA Antikörper | NFKBIA ELISA Kits | NFKBIA Proteine |
| NFkBP65 - p65: | NFkBP65 Antikörper | NFkBP65 ELISA Kits | NFkBP65 Proteine |
| NR2C2 - Nuclear Receptor Subfamily 2, Group C, Member 2: | NR2C2 Antikörper | NR2C2 ELISA Kits | NR2C2 Proteine |
| RIP2 (ROP Interactive Partner 2): | RIP2 Antikörper | ||
| UBE2V1 (Ubiquitin-Conjugating Enzyme E2 Variant 1): | UBE2V1 Antikörper | UBE2V1 ELISA Kits | UBE2V1 Proteine |
| UBE2N (Ubiquitin-Conjugating Enzyme E2N): | UBE2N Antikörper | UBE2N Proteine |
