MAIN TKCRs

Conserved sequences : a NTD Cys-rich region and a WSXWS motif.
The ligand induces dimerization of the TKCR, which in turn causes dimerization of the RCTK. The RCTK monomers undergo cross-phosphorylation : such activated RCTK can phosphorylate tyrosine residues on the TKCR (if the TKCR is multimeric, the b subunit only is phosphorylated). Suchb pY motifs on the TKCR recruit signaling molecules that are themselves phosphorylated by the TKCRs (IRSs, RTKs, STATs: phosphorylated STATs can create homodimers, heterodimers or heterotrimers. Different STATs have different specificities for different TKCRs)
Click here for their STP.
 
TKCR family
TKCR name
RCTKs
expressed on ..
ligand(s)
antagonists
agonists
interferon receptors IFNAR1 / IFN-aR / IFN-aRa / CD118 (multimeric) p130Jak1
p135Tyk2
IFN-a
IFN-b
IFN-k
IFN-w1
IFN-t
IFNAR2 / IFN-aR2 / IFN-aRbL (multimeric)  p130Jak1
p135Tyk2
IFN-a
IFN-b
IFN-k
IFN-w1
IFN-t
IL-28 and IL-29 R (multimeric : IL-28Ra + IL-10Rb) p130Jak1 IL-28A / IFN-l2
IL-28B / IFN-l3
IL-29 / IFN-l1
IFNGR1 / IFN-gR1 / IFN-gRa / CD119 (multimeric; IFN-g provides the NLS for nuclear transport of IFNGR-1 and STAT1a, which don't contain an intrinsic NLS.)  p130Jak1
p130Jak2
p135Tyk2
IFN-g
IFNGR2 (multimeric)  p130Jak1
p130Jak2
p135Tyk2
IFN-g
IL-10R (multimeric : CD210 / ILR10a + IL-10Rb) p130Jak1
p135Tyk2
IL-10
CD130 / gp130 IL-6R (multimeric : CD126 / IL-6Ra + CD130 / gp130 / IL-6Rb) p130Jak1
p130Jak2
p135Tyk2
IL-6
IL-11R (multimeric : IL-11Ra + IL-11Rb + CD130 / gp130) p130Jak1
p130Jak2
p135Tyk2
IL-11
IL-12R (multimeric : IL-12Rb1 / CD212 + IL-12Rb2) p130Jak1
p130Jak2
p135Tyk2
IL-12
G-CSFR / CD114 p130Jak1
p130Jak2
p135Tyk2
Syk
p53-56Lyn
G-CSF progenipoietin-4 (ProGP-4) (also for FLT-3)
LIFR (multimeric : LIFR + CD130 / gp130) p130Jak1
p130Jak2
p135Tyk2
LIF
CNTFR (multimeric : CD130 / gp130) p130Jak2
p135Tyk2
CNTF
OSMR (multimeric : OSMRb + CD130 / gp130) p130Jak1
p130Jak2
p135Tyk2
induced in activated monocytes, constitutive in epithelial cells  OsM
IL-31 (together with IL-31RA)
LEPR / OB-R Jak3 both AgRP/NPY- and a-MSH/CART-producing neurons of the arcuate nucleus; increases in the endometrium during the menstrual cycle secretory phase, decreases in subfertile women  leptin leptin peptide antagonist (LPA2)
CD131 / gp140 / bc IL-3R (multimeric : CD123 / IL-3Ra + CD131 / gp140 / bc + CD132 / gc) p130Jak1
p130Jak2
p53-56Lyn
IL-3
IL-5R (multimeric : CDw125 / IL-5Ra + CD131 / gp140 / bc) p130Jak1
p130Jak2
IL-5
GM-CSFR (multimeric : CD116 / c-fms / GMCSFRa + CD131 / gp140 / bc) p130Jak1
p130Jak2
GM-CSF
CD132 / gc IL-2R (multimeric : CD25 / IL-2Ra + CD122 / IL-2Rb + CD132 / gc) p130Jak1
Jak3
p56Lck
p59Fyn
IL-7
IL-4R type I (multimeric : CD124 / IL-4Ra + CD132 / gc) p130Jak1
Jak3
mast cells, resting T and B cells, macrophages, myeloid progenitors, stromal cells, fibroblasts, and hepatocytes IL-4
IL-7R (multimeric : CD127 + CD132 / gc) p130Jak1
Jak3
IL-2
IL-9R (multimeric : IL-9Ra + CD132 / gc p130Jak1
Jak3
p135Tyk2
IL-9
IL-13R (multimeric : CD213a1 / IL-13Ra1 + CD213a2 / IL-13Ra2 + CD132 / gc + CD24 (?))  p130Jak1
p130Jak2
Jak3
p135Tyk2
IL-13
IL-15R (multimeric : IL-15Ra + IL-15Rb + CD122 / IL-2Rb + CD132 / gc) p130Jak1
p130Jak2
Jak3
IL-15
IL-21R (multimeric : IL-21R + CD132 / gc) NK cells, T cells IL-21
IL-4R type II (multimeric : CD124 / IL-4Ra + CD213a1 / IL-13Ra1) p130Jak1
p130Jak2
Jak3
B cells, macrophages, mast cells IL-4
IL-13
Y119D
IL-17R / CD217 IL-17
IL-17BR IL-17B
IL-17E
IL-19R IL-19
IL-20R (multimeric : IL-20Ra + IL-20Rb) IL-20
IL-22R subepithelial myofibroblasts (SEMFs)ref IL-22
IL-23R (IL-23Ra + IL-12Rb1 / CD212) p130Jak2
p135Tyk2
IL-23
Iga / CD79a + Igb / CD79b Syk
CD3deg + CD247 / z chain ZAP70 Ag
CD4 p56Lck TcR
IL-16
CD8a or CD8b p56Lck TcR
CD16a / FcgRIIIA or CD16b / FcgRIIIB p56Lck
adipoR1 skeletal muscle, aortic endothelial cellref1, ref2 (higher) proteolytic cleavage fragment oconsisting of the globular C-terminal domain of adiponectin (gAd) >> full-length adiponectin (fAd)ref1, ref2, ref3
adipoR2 hepatocytes, aortic endothelial cellref1, ref2 (lower) adiponectin (intemediate affinity for both gAd and fAd)ref1, ref2, ref3
IL-31RA (together with OSMR) induced in activated monocytes, constitutive in epithelial cells  IL-31
imidazol(in)e receptors (I-Rs). ["imidazoline," by consensus (International Union of Pharmacology), includes imidazole, imidazoline, and related compounds] imidazoline receptor 1 (I1R / I1 / nischarin rostroventrolateral part of the brainstem, presynaptic (inhibit norepinephrine (NE) release from sympathetic nerve endings), lateral reticular nucleus, platelets, endocrine pancreas, heart, and kidney aganodine 
4-chloro-2-(2-imidazolin-2-yl-amino)-isoindoline (BDF 6143) 
1,3-di(2-tolyl)guanidine (DTG) 
benazoline 
clonidine (Catapres®, Catapres TTS®
p-iodoclonidine (PIC) 
cirazoline 
cis-/trans-dicyclopropylmethyl-(4,5-dimethyl-4,5-dihydro 
-3H-pyrrol-2-yl)-amine (LNP 509) 
2-(2-chloro-4-iodo-phenylamino)-5-methyl-pyrroline (LNP 911) 
4-chloro-2-(imidazolin-2-ylamino)-isoindoline (BDF 6143) 
idazoxan 
lofexidine (Britlofex®
moxonidine 
rilmenidine 
UK 14,304 
imidazole-4-acetic acid-ribotide (IAA-RP)ref
imidazole-4-acetic acid (IAA) 
efaroxan 
SKF 86466 
imidazoline receptor 2 (I2R / I2 idazoxan
GH receptor family hCS / hPL and hGH receptor (GHR) / STH receptor
  • STP through d3-GHR (a dominant allele which lacks exon 3 for which 50% of Europeans are hetero- or homozygous) homo- or heterodimers is 30% higher than through full-length GHR homodimersref
p130Jak2 hCS 1 / hPL
hCS 2
hGH / STH 1
hGH / STH 2
pegvisomant / B2036-PEG is a GH analogue that includes a single amino acid substitution at position 120 that generates the GHR antagonist. Additional changes include amino acid substitutions within binding site 1 and a further modification by the addition of polyethylene glycol moieties that increase the half-life and reduce the immunogenicity of the molecule. 
EPOR p130Jak1
p130Jak2
all regions of kidney, mesangial, proximal and distal tubular cells, endometrial epithelial cells in the secretory > proliferative phase  EPO
  • see erythropoiesis-stimulating agents (ESA)
  • PRL receptor p130Jak2 PRL
    THPO p130Jak1
    p135Tyk2
    mature platelets and megakaryocytes  thrombopoietin
  • PEG-MGDF : a pegylated, truncated form of hTPO was effective but induced the production of neutralizing antiTPO antibodies, resulting in thrombocytopenia in some recipients. The agent was therefore withdrawn from further clinical investigation
  • romiplostim / AMG531 (Nplate®; source : Amgen) consists of disulfide-bonded human IgG1 heavy-chain and kappa light-chain constant regions (an Fc fragment) with 2 identical TPO-binding domains covalently at residue 228 of the heavy chain with the use of a polyglycine. The Fc component extends the half-life of the molecule in the circulation. The peptide portion was selected by screening libraries of peptides that have no sequence homology with human thrombopoietin to find one with a tertiary structure that would allow it to bind to and activate the Mpl receptor. In healthy volunteers, AMG 531, a clear, colorless liquid administered by subcutaneous injection, increased platelet production and platelet counts and did not induce neutralizing or cross-reacting antibodies against TPOref1, ref2, ref3
  • eltrombopag (Promacta®, Revolade®; source : GlaxoSmith Kline) (p.o.)
  • Web resources :


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