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RTK Signalweg

Rezeptor Tyrosin Kinasen (RTKs) sind membrangebundene Kinasen, die nach der Bindung rezeptorspezifischer Liganden aktiviert werden. Sie stellen die größte Klasse der Membranrezeptoren dar, die Signalkaskaden durch ihre charakteristische Enzymaktivität auslösen. Diese Strukturen, Aktivierungsmechanismen und Schlüsselkomponenten der Signalwege sind bei Vielzellern stark konserviert. Beim Menschen sind 58 RTK bekannt, die entsprechend ihrer Topologie in 20 verschiedene Klassen eingeordnet werden.

Zu den aktivierenden Stimuli gehören eine Vielzahl von Wachstumsfaktoren, Hormonen und Zytokinen. Die meisten RTKs werden bei der Ligandenbindung aktiv und dimerisieren. Die aktivierte RTK phosphoryliert Aktivatoren der nachgeordneten Signalkaskaden, wie z. B. NF-kB-, MAPK- und Ca2+-abhängige Signalübertragungen, und des JAK-STAT-Signalwegs.

Dementsprechend beeinflussen RTKs eine große Bandbreite von Prozessen von der Dynamik des Zytoskeletts, Zellwachstum und Differenzierung bis hin zu Entzündung, Apoptose und Tumorprogression. Trotz der Vielfalt von Rezeptoren und Wirkungen sind nur wenige Kernprozesse an RTKs beteiligt. Aus diesem Grund ist die Durchführung quantitativer Analysen bestimmter Faktoren, wie z. B. die Expressionsgrenzen einer RTK, für das Verständnis der Signalübertragungsprozesse ebenso entscheidend wie für die Vorhersage qualitativer Ergebnisse.

Ligand

BDNF (Brain-Derived Neurotrophic Factor):

COL11A2 (Collagen, Type XI, alpha 2):

GDNF (Glial Cell Line Derived Neurotrophic Factor):

PDGFD (Platelet Derived Growth Factor D):

ATF2 (Activating Transcription Factor 2):

FGF1 (Fibroblast Growth Factor 1 (Acidic)):

FGF2 (Fibroblast Growth Factor 2 (Basic)):

FGF8 (Fibroblast Growth Factor 8 (Androgen-Induced)):

FLT3LG (Fms-Related tyrosine Kinase 3 Ligand):

GDNF (Glial Cell Line Derived Neurotrophic Factor):

HBEGF (Heparin-Binding EGF-Like Growth Factor):

HGF (Hepatocyte Growth Factor (Hepapoietin A, Scatter Factor)):

IGF1 (Insulin-Like Growth Factor 1):

PDGFB (Platelet Derived Growth Factor Subunit B):

PDGFA (Platelet Derived Growth Factor A):

PDGFC (Platelet-Derived Growth Factor C):

TGFA (Transforming Growth Factor, alpha):

TULP1 (Tubby Like Protein 1):

VEGFA (Vascular Endothelial Growth Factor A):

VEGFB (Vascular Endothelial Growth Factor B):

VEGFC (Vascular Endothelial Growth Factor C):

RTK

TYRO3 (TYRO3 Protein Tyrosine Kinase):

AATK (Apoptosis-Associated tyrosine Kinase):

AXL (AXL Receptor tyrosine Kinase):

MERTK (C-Mer Proto-Oncogene Tyrosine Kinase):

FGFR1 (Fibroblast Growth Factor Receptor 1):

FGFR2 (Fibroblast Growth Factor Receptor 2):

MST1R (Macrophage Stimulating 1 Receptor (C-Met-Related tyrosine Kinase)):

KIT (Mast/stem Cell Growth Factor Receptor):

ALK (Anaplastic Lymphoma Receptor tyrosine Kinase):

ROS1 (C-Ros Oncogene 1 , Receptor tyrosine Kinase):

CSF1R (Colony Stimulating Factor 1 Receptor):

DDR1 (Discoidin Domain Receptor tyrosine Kinase 1):

DDR2 (Discoidin Domain Receptor tyrosine Kinase 2):

EGFR (Epidermal Growth Factor Receptor):

FGFR3 (Fibroblast Growth Factor Receptor 3):

FGFR4 (Fibroblast Growth Factor Receptor 4):

FGFRL1 (Fibroblast Growth Factor Receptor-Like 1):

FLT1 (Fms-Related tyrosine Kinase 1 (VEGFR1)):

FLT3 (Fms-Related tyrosine Kinase 3):

FLT4 (Fms-Related Tyrosine Kinase 4):

INSRR (Insulin Receptor-Related Receptor):

IGF1R (Insulin-Like Growth Factor 1 Receptor):

LTK (Leukocyte Receptor tyrosine Kinase):

KIT (Mast/stem Cell Growth Factor Receptor):

MME (Membrane Metallo-Endopeptidase):

MUSK (Muscle, Skeletal, Receptor Tyrosine Kinase):

NTRK3 (Neurotrophic tyrosine Kinase, Receptor, Type 3):

PDGFRA (Platelet Derived Growth Factor Receptor alpha):

KCNH8 (Potassium Voltage-Gated Channel, Subfamily H (Eag-Related), Member 8):

PTK7 (PTK7 Protein tyrosine Kinase 7):

ROR1 (Receptor Tyrosine Kinase-Like Orphan Receptor 1):

ROR2 (Receptor Tyrosine Kinase-Like Orphan Receptor 2):

RYK (RYK Receptor-Like Tyrosine Kinase):

TEK (TEK Tyrosine Kinase, Endothelial):

TIE1 (tyrosine Kinase with Immunoglobulin-Like and EGF-Like Domains 1):

ERBB4 (V-Erb-A erythroblastic Leukemia Viral Oncogene Homolog 4 (Avian)):

ErbB2/Her2 (Receptor tyrosine-protein kinase erbB-2):

ERBB3 (Receptor Tyrosine-Protein Kinase ErbB-3):

Adaptors

SHC1 (SHC (Src Homology 2 Domain Containing) Transforming Protein 1):

SHC2 (SHC (Src Homology 2 Domain Containing) Transforming Protein 2):

GAB1 (GRB2-Associated Binding Protein 1):

GRB2 (Growth Factor Receptor-Bound Protein 2):

SHC3 (SHC (Src Homology 2 Domain Containing) Transforming Protein 3):

GEF

RASGRF1 (Ras Protein-Specific Guanine Nucleotide-Releasing Factor 1):

SOS1 (Son of Sevenless Homolog 1):

SOS2 (Son of Sevenless Homolog 2):

GTPase

RHOG (Ras Homolog Family Member G):

RAC2 (Ras-Related C3 Botulinum Toxin Substrate 2 (Rho Family, Small GTP Binding Protein Rac2)):

CDC42 (Cell Division Cycle 42 (GTP Binding Protein, 25kDa)):

HRAS (HRas proto-oncogene, GTPase):

RAC3 (Ras-Related C3 Botulinum Toxin Substrate 3 (Rho Family, Small GTP Binding Protein Rac3)):

Inhibitor

Kinase

AKT1 (V-Akt Murine Thymoma Viral Oncogene Homolog 1):

AKT2 (V-Akt Murine Thymoma Viral Oncogene Homolog 2):

AKT3 (V-Akt Murine Thymoma Viral Oncogene Homolog 3 (Protein Kinase B, Gamma)):

PIK3CA (Phosphoinositide-3-Kinase, Catalytic, alpha Polypeptide):

PDK1 (Pyruvate Dehydrogenase Kinase 1):

PDK2 (Pyruvate Dehydrogenase Kinase, Isozyme 2):

RPS6KB1 (Ribosomal Protein S6 Kinase, 70kDa, Polypeptide 1):

RPS6KB2 (Ribosomal Protein S6 Kinase, 70kDa, Polypeptide 2):

Messenger

Phosphatase

PPP3CA (Protein Phosphatase 3, Catalytic Subunit, alpha Isoform):

PTPN11 (Protein tyrosine Phosphatase, Non-Receptor Type 11):

PPP3CB (Protein Phosphatase 3, Catalytic Subunit, beta Isozyme):

PPP3CC (Protein Phosphatase 3, Catalytic Subunit, gamma Isozyme):

PPP3R1 (Protein Phosphatase 3, Regulatory Subunit B, alpha):

Phospholipase

Pro-apoptotic

BAD (BCL2-Associated Agonist of Cell Death):

Protease

Protein kinase

IKBKB (Inhibitor of kappa Light Polypeptide Gene Enhancer in B-Cells, Kinase beta):

IKBKG (Inhibitor of kappa Light Polypeptide Gene Enhancer in B-Cells, Kinase gamma):

ARAF (V-Raf Murine Sarcoma 3611 Viral Oncogene Homolog):

BRAF (B-Raf proto-oncogene, serine/threonine kinase):

RAF1 (V-Raf-1 Murine Leukemia Viral Oncogene Homolog 1):

Regulator

Transcription factor

NFATC1 (Nuclear Factor of Activated T-Cells, Cytoplasmic, Calcineurin-Dependent 1):

STAT1 (Signal Transducer and Activator of Transcription 1, 91kDa):

STAT3 (Signal Transducer and Activator of Transcription 3 (Acute-Phase Response Factor)):

NFAT5 (Nuclear Factor of Activated T-Cells 5, Tonicity-Responsive):

NFAT1 (Nuclear Factor of Activated T-Cells, Cytoplasmic, Calcineurin-Dependent 2):

NFATC3 (Nuclear Factor of Activated T-Cells, Cytoplasmic, Calcineurin-Dependent 3):

NFATC4 (Nuclear Factor of Activated T-Cells, Cytoplasmic, Calcineurin-Dependent 4):

NFKB1 (Nuclear Factor of kappa Light Polypeptide Gene Enhancer in B-Cells 1):

STAT5A (Signal Transducer and Activator of Transcription 5A):

STAT5B (Signal Transducer and Activator of Transcription 5B):

RELB (V-Rel Reticuloendotheliosis Viral Oncogene Homolog B):

Others

ARPC1B (Actin Related Protein 2/3 Complex, Subunit 1B, 41kDa):

CYFIP2 (Cytoplasmic FMR1 Interacting Protein 2):

ARPC2 (Actin Related Protein 2/3 Complex, Subunit 2, 34kDa):

ARPC3 (Actin Related Protein 2/3 Complex, Subunit 3, 21kDa):

ARPC4 (Actin Related Protein 2/3 Complex, Subunit 4, 20kDa):

ARPC5 (Actin Related Protein 2/3 Complex, Subunit 5, 16kDa):

ACTR3 (ARP3 Actin-Related Protein 3):

BRK1 (BRICK1, SCAR/WAVE Actin-Nucleating Complex Subunit):

WASF1 (WAS Protein Family, Member 1):

WASF2 (WAS Protein Family, Member 2):

WASF3 (WAS Protein Family, Member 3):

WIPF1 (WAS/WASL Interacting Protein Family, Member 1):

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