: 
Ligand-induced receptor dimerization (only InsR is already dimerized before ligand binding !) is inhibited by :
Ligand binding is inhibited by suramin,
a hexasulfonated naphthylurea compound of 1429 Da that was used
initially as a drug for the treatment of trypanosomiasis :
Ligand-induced receptor dimerization (only InsR is already dimerized before
ligand binding !) is inhibited by :
and an inhibitor of protein
serine/threonine
kinases))
-containing proteins. . |
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| CD220 / InsR (also activates STAT1 and STAT3) | brain neurons (including arcuate nucleus) | insulin |
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| CD221 / IGF-1R | NSILA(S)-1 / SM-C / IGF-1 |
inhibitor of the IGF-IR kinaseref :
|
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| CD115 / M-CSFR / CSF-1R (also activates STAT3 and STAT5) | monocytes, macrophages |
M-CSF / CSF-1 IL-34 |
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| HGF receptor / c-Met | epithelial cells and melanocytes |
HGF / scatter factor neurturin |
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| tyrosine kinase with immunoglobulin and epidermal growth factor 1 (Tie-1 / TIE) | Ang-1 Ang-2 Ang-3 Ang-4 |
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| CD202b / tyrosine kinase with immunoglobulin and epidermal growth factor 1 (Tie-2) | Ang-1 Ang-2 Ang-3 Ang-4 |
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| FGFR1 / fms2 (9 isoforms) (also activates STAT3) | FGF/HBGF 1-23, including FGF-1 / aFGF, FGF2 / bFGF, FGF-7 / KGF,
... |
nintedanib / BIBF 1120 (Vargatef®; triple angiokinase inhibitor that also simultaneously acts on VEGFR and PDGFR) | |||
| FGFR2 (13 isoforms) (also activates STAT3) | FGF/HBGF 1-23, including FGF-1 / aFGF, FGF2 / bFGF, FGF-7 / KGF,
... |
||||
| FGFR3 (2 isoforms) (also activates STAT3) | FGF/HBGF 1-23, including FGF-1 / aFGF, FGF2 / bFGF, FGF-7 / KGF,
... |
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| FGFR4 (2 isoforms) (also activates STAT3) | FGF/HBGF 1-23, including FGF-1 / aFGF, FGF2 / bFGF, FGF-7 / KGF,
... |
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| FLT-1 / VEGFR1 | VEGF-A121, 165, 189 or 206 PlGF VEGF-B |
|
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| FLT-3 | a high proportion of acute
myeloid
leukemia (AML)
and B-lineage
acute
lymphocytic leukemia (ALL)
cells, hematopoietic
stem
cells (HSCs),
brain, placenta and liver |
FLT3L |
progenipoietin-4 (ProGP-4) (also for G-CSFR) |
ref)
|
|
| FLK-1 / VEGFR2 / KDR | VEGF-A121, 165, 189 or 206 VEGF-C VEGF-D VEGF-E |
ref) |
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| FLT-4 / VEGFR3 | lymphatic
endothelial cells |
VEGF-C VEGF-D |
|
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| ERBB1 / c-ERBB / EGF receptor (EGFR) / HER-1 (needs cleavage on the ECM side by ADAM to be activated; also activates STAT1, STAT3, and STAT5) | EGF TGFa betacellulin neuregulin 1 |
gefitinib / ZD1839
(Iressa©; IC50
= 0.023-0.069 mM; IC50 for
ligand-induced cell growth = 0.080 mM;
source : AstraZeneca; side effect :
interstitial pneumonia) erlotinib / OSI-774 (Tarceva©; source : Genentech) lapatinib / EGF105084 (Tykerb©; source : GSK) ZD6474 CI1033 GW572016 PKI166 EKB-569 leflunomide (Arava©) and it's metabolite, A771726 / teriflunomide |
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| ERBB2 / NEU / HER-2 (to function it must dimerize with another member of the ERBB family) | neuregulin 1 (binds ERBB2 /
ERBB3 heterodimer) |
gefitinib lapatinib GW572016 PKI166 |
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| ERBB3 / HER-3 (decoy receptor as it lacks Tyr kinase activity) | neuregulin 1 (binds ERBB2 /
ERBB3 heterodimer) neuregulin 2 |
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| ERBB4 / HER-4 | betacellulin neuregulin 1 neuregulin 2 intramembrane binding with the transmembrane domain of ASGP2 |
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| PDGFR (multimeric : CD140a / a + CD140b / b) (also activates STAT1, STAT3, and STAT5) | PDGF |
|
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| relaxin receptor | RLX1 RLX2 RLX3 |
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| CD117 / c-KIT | SCF |
ref) |
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| TRK family members are variably expressed throughout the central and peripheral nervous systems | TrkA / neurotrophic tyrosine kinase, receptor, type 1 autophosphorylates on tyrosine residues (Tyr490, Tyr674, Tyr675, Tyr751, and Tyr785) | neurotrophins / neurotrophic factors : | |||
| TrkB | pre- and postsynaptic neurons of excitatory synaptic transmission in the CA1 region of the hippocampus | neurotrophins / neurotrophic factors : | |||
| TrkC | neurotrophins / neurotrophic factors :
|
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| TrkE / discoidin domain receptor family, member 1 | |||||
| p75NTR | neurotrophins / neurotrophic factors : | ||||
| RET | nociceptors | neurotrophins / neurotrophic factors :
|
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| receptor for advanced glycation endproducts (RAGE) (needs cleavage on the ECM side by an ADAM to be activated) | peripheral neurons, vascular
endothelial cells
and pericytes, synovial
fibroblasts |
|
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| muscle-specific kinase (MuSK) | early myotomes and developing muscle, then dramatically down-regulated in mature muscle, where it remains prominent only at the NMJ (the only known RTK that localizes to the NMJ); induced throughout the adult myofiber after denervation, block of electrical activity, or physical immobilization. | agrin |
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| anaplastic lymphoma kinase (Alk) | Jelly belly
(Jeb) |
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| amphoterin | |||||
| EPH receptors typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. They are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. | EphA1 | Ephrin-A1 Ephrin-A2 Ephrin-A3 Ephrin-A4 Ephrin-A5 |
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| EphA2 | Ephrin-A1 Ephrin-A2 Ephrin-A3 Ephrin-A4 Ephrin-A5 |
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| EphA3 | Ephrin-B2 |
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| EphA4 | Ephrin-A1 Ephrin-A2 Ephrin-A3 Ephrin-A4 Ephrin-A5 |
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| EphA5 | Ephrin-A1 Ephrin-A2 Ephrin-A3 Ephrin-A4 Ephrin-A5 |
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| EphA7 | Ephrin-A1 Ephrin-A2 Ephrin-A3 Ephrin-A4 Ephrin-A5 |
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| EphA8 | Ephrin-A2 Ephrin-A3 Ephrin-A5 |
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| EphB1 | Ephrin-B1 Ephrin-B2 Ephrin-B3 |
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| EphB2 | Ephrin-B1 Ephrin-B2 Ephrin-B3 |
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| EphB3 | Ephrin-B1 Ephrin-B2 Ephrin-B3 |
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| EphB4 | Ephrin-B2 |
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| EphB6 (decoy receptor : lacks the kinase activity) | Ephrin-B1 Ephrin-B2 Ephrin-B3 |
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| Membrane-bound receptors generate soluble ligand binding domains either by proteolytic cleavage of the extracellular domain or alternative mRNA splicing yielding a secreted protein. MERTK is in a receptor tyrosine kinase family with Axl and Tyro-3, and all 3 receptors share the Gas6 ligand. Mer regulates macrophage activation, promotes apoptotic cell engulfment, and supports platelet aggregation and clot stability in vivo. The membrane-bound Mer protein is cleaved in the extracellular domain via a MMP. The cleavage results in the production of a soluble Mer protein released in a constitutive manner from cultured cells. Significant amounts of the soluble Mer protein were also detected in human plasma, suggesting its physiological relevance. Cleavage of Mer was enhanced by treatment with LPS and PMA, and was specifically inhibited by a TNF converting enzyme metalloprotease inhibitor. As a decoy for Gas6, soluble Mer prevented Gas6 mediated stimulation of membrane-bound Mer. The inhibition of Gas6 activity by soluble Mer led to defective macrophage-mediated engulfment of apoptotic cells. Furthermore, soluble Mer decreased platelet aggregation in vitro and prevented fatal collagen/epinephrine induced thromboembolism in mice, suggesting a potential therapeutic use for soluble Mer in the treatment of clotting disordersref | |||||
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