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:

  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 Membran 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].   More...

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).
Antigene in dieser Kategorie:
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): CD8A Antikörper    
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 ELISA Kits HLADQA1 Proteine
HLA-DQA2 - Major Histocompatibility Complex, Class II, DQ alpha 2: HLA-DQA2 Antikörper   HLA-DQA2 Proteine
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 ELISA Kits TMEM189 Proteine

Adaptor Proteins and Regulators

Antigene in dieser Kategorie:
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 ELISA Kits 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)

Antigene in dieser Kategorie:
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): PTEN Antikörper    
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 ELISA Kits RASSF5 Proteine
RASGRP1 - RAS Guanyl Releasing Protein 1 (Calcium and DAG-Regulated): RASGRP1 Antikörper RASGRP1 ELISA Kits RASGRP1 Proteine
RASGRP2 (RAS Guanyl Releasing Protein 2 (Calcium and DAG-Regulated)): RASGRP2 Antikörper RASGRP2 ELISA Kits RASGRP2 Proteine
SOS1 (Son of Sevenless Homolog 1 (Drosophila)): SOS1 Antikörper SOS1 ELISA Kits 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 ELISA Kits 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....
Antigene in dieser Kategorie:
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 ELISA Kits 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

Antigene in dieser Kategorie:
BCL10 (B-Cell CLL/lymphoma 10): BCL10 Antikörper BCL10 ELISA Kits BCL10 Proteine
CARD11 (Caspase Recruitment Domain Family, Member 11): CARD11 Antikörper CARD11 ELISA Kits 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 ELISA Kits UBE2N Proteine
RELA (V-Rel Reticuloendotheliosis Viral Oncogene Homolog A (Avian)):     RELA Proteine