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RTK Signaling

Receptor Tyrosine Kinases (RTKs) are membrane bound kinases that are activated upon binding of receptor specific ligands. They make up the largest class of membrane receptors that trigger signaling cascades through their inherent enzymatic activity. These structures, activation mechanisms and key components of the signaling pathways are highly conserved in metazoans. There are 58 known RTKs in humans, which are grouped into 20 classes depending on topology.

RTKs are fairly promiscuous receptors, and activating stimuli comprise a plethora of growth factors, hormones, and cytokines. Most RTKs form dimers and become active upon ligand binding. The active RTK phosphorylates activators of downstream signaling cascades such as NF-kB, MAPK, Ca2+ dependent signaling, and the JAK-STAT pathway.

RTKs affect a wide spectrum of processes ranging from cytoskeleton dynamics, cell growth and differentiation to inflammation, apoptosis, and tumor progression. In spite of the exceptionally high variety of receptors and outcomes, RTKs engage only a limited set of core processes. Therefore, quantitative analysis of factors like an RTK’s expression profile are crucial for the understanding of the signaling processes and predicting qualitative outcomes.

Ligand

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

RTK

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

ALK (Anaplastic Lymphoma Receptor tyrosine Kinase):

PDGFRA (Platelet-Derived Growth Factor Receptor, alpha Polypeptide):

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

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

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

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):

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

GEF

GTPase

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

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

Inhibitor

Kinase

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

PIK3CG (Phosphoinositide-3-Kinase, Catalytic, gamma Polypeptide):

Messenger

Phosphatase

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

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

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

Phospholipase

Pro-apoptotic

Protease

Protein kinase

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):

Others

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

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