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Signalisation RTK

Les récepteurs tyrosine kinase (RTK) sont des kinases liées à la membrane qui sont activées lorsque les ligands spécifiques aux récepteurs se lient. Ils constituent la plus grande classe de récepteurs de membrane qui provoquent des cascades de signalisation via leur activité enzymatique inhérente. Ces structures, mécanismes d’activation et composants-clé des voies de signalisation sont hautement conservés chez les métazoaires. Chez l’être humain on connaît 58 RTK, groupées en 20 classes selon leur topologie.

Les stimuli activateurs comprennent de nombreux facteurs de croissance, hormones et cytokines. La plupart des RTK se dimérisent et deviennent actives lorsque le ligand se lie. La RTK activée provoque la phosphorylation des activateurs de cascades de signalisation descendantes telles que la signalisation dépendante de NF-kB, MAPK, Ca2+ ainsi que la voie JAK-STAT.

Les RTK affectent donc un vaste éventail de processus incluant la dynamique du cytosquelette, la croissance et la différenciation cellulaires, l’apoptose et la progression tumorale. En dépit de cette variété de récepteurs et de résultats, les RTK n’engagent qu’un nombre limité de processus principaux. Il est donc crucial d’analyser de manière quantitative des facteurs tels que la limite d’expression d’une RTK afin de comprendre les processus de signalisation et prévoir des résultats qualitatifs.

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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