Literature DB >> 24528241

The Concise Guide to PHARMACOLOGY 2013/14: catalytic receptors.

Stephen P H Alexander¹, Helen E Benson, Elena Faccenda, Adam J Pawson, Joanna L Sharman, Michael Spedding, John A Peters, Anthony J Harmar.

Abstract

The Concise Guide to PHARMACOLOGY 2013/14 provides concise overviews of the key properties of over 2000 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.12444/full. Catalytic receptors are one of the seven major pharmacological targets into which the Guide is divided, with the others being G protein-coupled receptors, ligand-gated ion channels, ion channels, nuclear hormone receptors, transporters and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. A new landscape format has easy to use tables comparing related targets. It is a condensed version of material contemporary to late 2013, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in previous Guides to Receptors and Channels. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and the Guide to Receptors and Channels, providing a permanent, citable, point-in-time record that will survive database updates.

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Year: 2013 PMID： 24528241 PMCID： PMC3892291 DOI： 10.1111/bph.12449

Source DB: PubMed Journal: Br J Pharmacol ISSN： 0007-1188 Impact factor: 8.739

An Introduction to Catalytic Receptors

Catalytic receptors are cell-surface proteins, usually dimeric in nature, which typically encompass ligand binding and functional domains in one polypeptide chain. The ligand binding domain is placed on the extracellular surface of the plasma membrane and separated from the functional domain by a single transmembrane-spanning domain of 20-25 hydrophobic amino acids. The functional domain on the intracellular face of the plasma membrane has catalytic activity, or interacts with particular enzymes, giving the superfamily of receptors its name. Endogenous agonists of the catalytic receptor superfamily are peptides or proteins, the binding of which may induce dimerization of the receptor, which is the functional version of the receptor. Amongst the catalytic receptors, particular subfamilies may be readily identified dependent on the function of the enzymatic portion of the receptor. The smallest group is the particulate guanylyl cyclases of the natriuretic peptide receptor family. The most widely recognized group is probably the receptor tyrosine kinase (RTK) family, epitomized by the neurotrophin receptor family, where a crucial initial step is the activation of a signalling cascade by autophosphorylation of the receptor on intracellular tyrosine residue(s) catalyzed by enzyme activity intrinsic to the receptor. A third group is the extrinsic protein tyrosine kinase receptors, where the catalytic activity resides in a separate protein from the binding site. Examples of this group include the GDNF receptor families, where one, catalytically silent, member of the heterodimer is activated upon binding the ligand, causing the second member of the heterodimer, lacking ligand binding capacity, to initiate signaling through tyrosine phosphorylation. A fourth group, the receptor threonine/serine kinase (RTSK) family, exemplified by TGF-β and BMP receptors, has intrinsic serine/threonine protein kinase activity in the heterodimeric functional unit. A fifth group is the receptor tyrosine phosphatases (RTP), which generally appear to lack cognate ligands, but may be triggered by events such as cell:cell contact and have identified roles in the skeletal, hematopoietic and immune systems. A new group of catalytic receptors for the Guide is the integrins, which have roles in cell : cell communication, often associated with signalling in the blood.

Nomenclature	Interleukin-2 receptor	Interleukin-4 receptor type I	Interleukin-4 receptor type II	Interleukin-7 receptor	Interleukin-9 receptor
Subunits	Interleukin-2 receptor α subunit (Ligand-binding subunit), Interleukin-2 receptor β subunit (Ligand-binding subunit), Interleukin-2 receptor γ subunit (Other subunit)	Interleukin 4 receptor (Ligand-binding subunit), Interleukin-2 receptor γ subunit (Other subunit)	Interleukin 4 receptor (Ligand-binding subunit), Interleukin 13 receptor, α1 (Other subunit)	Interleukin 7 receptor (Ligand-binding subunit), Interleukin-2 receptor γ subunit (Other subunit)	Interleukin 9 receptor (Ligand-binding subunit), Interleukin-2 receptor γ subunit (Other subunit)
Endogenous agonists	IL-2 (IL2, P60568)	IL-4 (IL4, P05112)	IL-13 (IL13, P35225), IL-4 (IL4, P05112)	IL-7 (IL7, P13232)	IL-9 (IL9, P15248)
Endogenous antagonists	IL-1 receptor antagonist (IL1RN, P18510)	–	–	–	–
Selective antagonists	AF12198 1, Ro264550 3	–	–	–	–

Nomenclature	Interleukin 13 receptor, α2	Interleukin-15 receptor	Interleukin-21 receptor	Thymic stromal lymphopoietin receptor
HGNC, UniProt	IL13RA2, Q14627	–	–	–
Subunits	–	Interleukin-2 receptor β subunit (Ligand-binding subunit), Interleukin 15 receptor, α subunit (Ligand-binding subunit), Interleukin-2 receptor γ subunit (Other subunit)	Interleukin 21 receptor (Ligand-binding subunit), Interleukin-2 receptor γ subunit (Other subunit)	Interleukin 7 receptor (Ligand-binding subunit), Cytokine receptor-like factor 2 (Other subunit)
Endogenous agonists	–	IL-15 (IL15, P40933)	IL-21 (IL21, Q9HBE4)	TSLP (TSLP, Q969D9)
Comment	Decoy receptor that binds IL-13 (IL13, P35225) as a monomer.	–	–	–

Nomenclature	Interleukin-3 receptor	Interleukin-5 receptor	Granulocyte macrophage colony-stimulating factor receptor
Subunits	Interleukin 3 receptor, α subunit (Ligand-binding subunit), Cytokine receptor common β subunit (Other subunit)	Interleukin 5 receptor, α subunit (Ligand-binding subunit), Cytokine receptor common β subunit (Other subunit)	GM-CSF receptor, α subunit (Ligand-binding subunit), Cytokine receptor common β subunit (Other subunit)
Endogenous agonists	IL-3 (IL3, P08700)	IL-5 (IL5, P05113)	G-CSF (CSF3, P09919), GM-CSF (CSF2, P04141)
Selective antagonists	–	YM90709 2	–

Nomenclature	Interleukin-6 receptor	Interleukin-11 receptor	Interleukin-31 receptor	Ciliary neutrophic factor receptor
Subunits	Interleukin-6 receptor, α subunit (Ligand-binding subunit), Interleukin-6 receptor, β subunit (Other subunit)	Interleukin-11 receptor, α subunit (Ligand-binding subunit), Interleukin-6 receptor, β subunit (Other subunit)	Interleukin-31 receptor, α subunit (Ligand-binding subunit), Oncostatin M-specific receptor, β subunit (Other subunit)	Ciliary neurotrophic factor receptor α subunit (Ligand-binding subunit), Leukemia inhibitory factor receptor (Other subunit), Interleukin-6 receptor, β subunit
Endogenous agonists	IL-6 (IL6, P05231)	IL-11 (IL11, P20809)	IL-31 (IL31, Q6EBC2)	CNTF (CNTF, P26441), CRCF1/CLCF1 heterodimer (CRLF1, CLCF1, O75462, Q9UBD9)

Nomenclature	Leptin receptor	Leukemia inhibitory factor receptor	Oncostatin-M receptor	Interleukin-27 receptor
HGNC, UniProt	LEPR, P48357	–	–	–
Subunits	–	Leukemia inhibitory factor receptor (Ligand-binding subunit), Interleukin-6 receptor, β subunit (Other subunit)	Oncostatin M-specific receptor, β subunit (Ligand-binding subunit), Interleukin-6 receptor, β subunit (Other subunit)	Interleukin 27 receptor, alpha (Ligand-binding subunit), Interleukin-6 receptor, β subunit (Other subunit)
Endogenous agonists	leptin (LEP, P41159)	CTF1 (CTF1, Q16619), LIF (LIF, P15018), OSM (OSM, P13725)	OSM (OSM, P13725)	IL-27 (IL27, EBI3, Q14213, Q8NEV9)

Nomenclature	Interleukin-12 receptor, β2 subunit	Interleukin 23 receptor
HGNC, UniProt	IL12RB2, Q99665	IL23R, Q5VWK5

Nomenclature	Eythropoietin receptor	Granulocyte colony-stimulating factor receptor	Growth hormone receptor	Prolactin receptor	Thrombopoietin receptor
HGNC, UniProt	EPOR, P19235	CSF3R, Q99062	GHR, P10912	PRLR, P16471	MPL, P40238
Endogenous agonists	erythropoietin (EPO, P01588)	G-CSF (CSF3, P09919)	growth hormone 1 (GH1, P01241), growth hormone 2 (GH2, P01242)	choriomammotropin (CSH1, CSH2, P01243), chorionic somatomammotropin hormone-like 1 (CSHL1, Q14406), prolactin (PRL, P01236)	thrombopoietin (THPO, P40225)

Nomenclature	Interferon-α/β receptor	Interferon-γ receptor
Subunits	interferon α/β receptor 1 (Ligand-binding subunit), Interferon α/β receptor 2 (Other subunit)	Interferon γ receptor 1 (Ligand-binding subunit), Interferon γ receptor 2 (Other subunit)
Endogenous agonists	IFN-α10 (IFNA10, P01566), IFN-α1/13 (IFNA1, IFNA13, P01562), IFN-α14 (IFNA14, P01570), IFN-α16 (IFNA16, P05015), IFN-α17 (IFNA17, P01571), IFN-α2 (IFNA2, P01563), IFN-α21 (IFNA21, P01568), IFN-α4 (IFNA4, P05014), IFN-α5 (IFNA5, P01569), IFN-α6 (IFNA6, P05013), IFN-α7 (IFNA7, P01567), IFN-α8 (IFNA8, P32881), IFN-β (IFNB1, P01574), IFN-κ (IFNK, Q9P0W0), IFN-ω (IFNW1, P05000)	IFN-γ (IFNG, P01579)

Nomenclature	Interleukin-10 receptor	Interleukin-20 receptor	Interleukin-22α1/20β heteromer	Interleukin-22α1/10β heteromer	Interleukin-22 receptor α2	Interferon-λ receptor 1
HGNC, UniProt	–	–	–	–	IL22RA2, Q969J5	–
Subunits	Interleukin 10 receptor, α subunit (Ligand-binding subunit), Interleukin 10 receptor, β subunit (Other subunit)	Interleukin 20 receptor, α subunit (Ligand-binding subunit), Interleukin 20 receptor, β subunit (Other subunit)	Interleukin 20 receptor, β subunit (Ligand-binding subunit), Interleukin 22 receptor, α1 subunit (Ligand-binding subunit)	Interleukin 10 receptor, β subunit (Ligand-binding subunit), Interleukin 22 receptor, α1 subunit (Ligand-binding subunit)	–	Interferon-λ receptor 1 (Ligand-binding subunit), Interleukin 10 receptor, β subunit (Other subunit)
Endogenous agonists	IL-10 (IL10, P22301)	IL-19 (IL19, Q9UHD0), IL-20 (IL20, Q9NYY1), IL-24 (IL24, Q13007)	IL-20 (IL20, Q9NYY1), IL-24 (IL24, Q13007)	IL-22 (IL22, Q9GZX6)	–	IFN-λ1 (IFNL1, Q8IU54), IFN-λ2 (IFNL2, Q8IZJ0), IFN-λ3 (IFNL3, Q8IZI9)
Comment	–	–	–	–	Soluble decoy receptor that binds IL-22 (IL22, Q9GZX6) as a monomer	–

Nomenclature	Interleukin-1 receptor, type I	Interleukin-33 receptor	Interleukin-36 receptor	Interleukin-1 receptor, type II	Interleukin-18 receptor
Subunits	Interleukin 1 receptor, type I (Ligand-binding subunit), IL-1 receptor accessory protein (Other subunit)	Interleukin-1 receptor-like 1 (Ligand-binding subunit), IL-1 receptor accessory protein (Other subunit)	Interleukin-1 receptor-like 2 (Ligand-binding subunit), IL-1 receptor accessory protein (Other subunit)	Interleukin 1 receptor, type II (Ligand-binding subunit), IL-1 receptor accessory protein (Other subunit)	Interleukin-18 1 (Ligand-binding subunit), IL-18 receptor accessory protein (Other subunit)
Endogenous agonists	IL-1α (IL1A, P01583), IL-1β (IL1B, P01584)	IL-33 (IL33, O95760)	IL-36α (IL36A, Q9UHA7), IL-36β (IL36B, Q9NZH7), IL-36γ (IL36G, Q9NZH8),	–	IL-18 (IL18, Q14116), IL-37 (IL37, Q9NZH6)
Endogenous antagonists	IL-1 receptor antagonist (IL1RN, P18510)	–	IL-36 receptor antagonist (IL36RN, Q9UBH0)	–	–
Selective antagonists	AF12198 1	–	–	–	–
Comment	–	–	IL-36 receptor antagonist (IL36RN, Q9UBH0) is a highly specific antagonist of the response to IL-36γ (IL36G, Q9NZH8)	Decoy receptor that binds IL-1α (IL1A, P01583), IL-1β (IL1B, P01584) and IL-1 receptor antagonist (IL1RN, P18510)	–

Nomenclature	Interleukin-17 receptor	Interleukin-25 receptor	Interleukin-17C receptor	Interleukin-17 receptor D
HGNC, UniProt	–	–	–	IL17RD, Q8NFM7
Subunits	Interleukin 17 receptor A (Ligand-binding subunit), interleukin 17 receptor C (Other subunit)	Interleukin 17 receptor B (Ligand-binding subunit), Interleukin 17 receptor A (Other subunit)	Interleukin 17 receptor E (Ligand-binding subunit), Interleukin 17 receptor A (Other subunit)	–
Endogenous agonists	IL-17A (IL17A, Q16552), IL-17A/IL-17F (IL17F, IL17A, Q16552, Q96PD4), IL-17F (IL17F, Q96PD4)	IL-17B (IL17B, Q9UHF5), IL-25 (IL25, Q9H293)	IL-17C (IL17C, Q9P0M4)	The endogenous agonist for this receptor is unknown

Nomenclature	GDNF family receptor α1	GDNF family receptor α2	GDNF family receptor α3	GDNF family receptor α4
Common abbreviation	GFRα1	GFRα2	GFRα3	GFRα4
HGNC, UniProt	GFRA1, P56159	GFRA2, O00451	GFRA3, O60609	GFRA4, Q9GZZ7
Potency order	GDNF (GDNF, P39905) > NRTN (NRTN, Q99748) > ARTN (ARTN, Q5T4W7)	NRTN (NRTN, Q99748) > GDNF (GDNF, P39905)	ARTN (ARTN, Q5T4W7)	PSPN (PSPN, O60542)
Radioligands (K_d)	[125I]GDNF (rat) (3x10^-12 – 6.3x10^-11 M) 4,6	–	–	–

Nomenclature	Subunits	Ligands	Selective inhibitors (pIC₅₀)	Comment
α1β1	integrin, alpha 1 subunit, integrin, beta 1 subunit (fibronectin receptor, beta polypeptide, antigen CD29 includes MDF2, MSK12)	collagen, laminin	obtustatin (9.1) 11	–
α2β1	integrin, alpha 2 subunit (CD49B, alpha 2 subunit of VLA-2 receptor), integrin, beta 1 subunit (fibronectin receptor, beta polypeptide, antigen CD29 includes MDF2, MSK12)	collagen, laminin, thrombospondin	TCI15 (7.9) 13	–
αIIbβ3	integrin, alpha 2b subunit (platelet glycoprotein IIb of IIb/IIIa complex, antigen CD41), integrin, beta 3 subunit (platelet glycoprotein IIIa, antigen CD61)	fibrinogen, fibronectin, von Willebrand factor, vitronectin, thrombospondin	abciximab, eptifibatide, G4120 12, GR144053, Syk inhibitor III 14, tirofiban	–
α4β1	integrin, alpha 4 subunit (antigen CD49D, alpha 4 subunit of VLA-4 receptor), integrin, beta 1 subunit (fibronectin receptor, beta polypeptide, antigen CD29 includes MDF2, MSK12)	fibronectin, VCAM-1, osteopontin, thrombospondin	natalizumab, TCS2314, BIO1211 (8.3 – 9.0) 9	LDV-FITC is used as a probe at this receptor
αLβ2	integrin, alpha L subunit (antigen CD11A (p180), lymphocyte function-associated antigen 1; alpha polypeptide), integrin, beta 2 subunit (complement component 3 receptor 3 and 4 subunit)	ICAM-1, ICAM-2	efalizumab, A286982 (7.4 – 7.5) 10	–
αVβ3	integrin, alpha V subunit, integrin, beta 3 subunit (platelet glycoprotein IIIa, antigen CD61)	vitronectin, fibronectin, fibrinogen, osteopontin, von Willebrand factor, thrombospondin, tenascin	etaracizumab, echistatin (11.7) 8, P11 (11.6) 8, cilengitide (8.5) 7	–

Nomenclature	HGNC, UniProt
integrin, alpha 1 subunit	ITGA1, P56199
integrin, alpha 2 subunit (CD49B, alpha 2 subunit of VLA-2 receptor)	ITGA2, P08514
integrin, alpha 2b subunit (platelet glycoprotein IIb of IIb/IIIa complex, antigen CD41)	ITGA2B, P17301
integrin, alpha 3 subunit (antigen CD49C, alpha 3 subunit of VLA-3 receptor)	ITGA3, P26006
integrin, alpha 4 subunit (antigen CD49D, alpha 4 subunit of VLA-4 receptor)	ITGA4, P13612
integrin, alpha 5 subunit (fibronectin receptor, alpha polypeptide)	ITGA5, P08648
integrin, alpha 6 subunit	ITGA6, P23229
integrin, alpha 7 subunit	ITGA7, Q13683
integrin, alpha 8 subunit	ITGA8, P53708
integrin, alpha 9 subunit	ITGA9, Q13797
integrin, alpha 10 subunit	ITGA10, O75578
integrin, alpha 11 subunit	ITGA11, Q9UKX5
integrin, alpha D subunit	ITGAD, Q13349
integrin, alpha E subunit (antigen CD103, human mucosal lymphocyte antigen 1; alpha polypeptide)	ITGAE, P38570
integrin, alpha L subunit (antigen CD11A (p180), lymphocyte function-associated antigen 1; alpha polypeptide)	ITGAL, P20701
integrin, alpha M subunit (complement component 3 receptor 3 subunit)	ITGAM, P11215
integrin, alpha V subunit	ITGAV, P06756
integrin, alpha X subunit (complement component 3 receptor 4 subunit)	ITGAX, P20702

Nomenclature	HGNC, UniProt
integrin, beta 1 subunit (fibronectin receptor, beta polypeptide, antigen CD29 includes MDF2, MSK12)	ITGB1, P05556
integrin, beta 2 subunit (complement component 3 receptor 3 and 4 subunit)	ITGB2, P05107
integrin, beta 3 subunit (platelet glycoprotein IIIa, antigen CD61)	ITGB3, P05106
integrin, beta 4 subunit	ITGB4, P16144
integrin, beta 5 subunit	ITGB5, P18084
integrin, beta 6 subunit	ITGB6, P18564
integrin, beta 7 subunit	ITGB7, P26010
integrin, beta 8 subunit	ITGB8, P26012

Nomenclature	NPR-A	NPR-B	NPR-C	guanylate cyclase 2C (heat stable enterotoxin receptor)
HGNC, UniProt	NPR1, P16066	NPR2, P20594	NPR3, P17342	GUCY2C, P25092
Potency order	ANP (NPPA, P01160) ≥ BNP (NPPB, P16860) >> CNP (NPPC, P23582) 27	CNP (NPPC, P23582) >> ANP (NPPA, P01160) >> BNP (NPPB, P16860) 27	ANP (NPPA, P01160) > CNP (NPPC, P23582) ≥ BNP (NPPB, P16860) 27	uroguanylin (GUCA2B, Q16661) > guanylin (GUCA2A, Q02747)
Endogenous agonists	ANP (NPPA, P01160) (Selective) 26, BNP (NPPB, P16860) (Selective) 26	CNP (NPPC, P23582) (Selective) 27	osteocrin (OSTN, P61366) (Selective) 23	–
Selective agonists	sANP 26	–	cANF4-23 22	E. coli heat-stable enterotoxin (STa), linaclotide 18
Selective antagonists	anantin 29, A-71915 (pK_i 9.2 – 9.5) 15, [Asu7,23']β-ANP-(7-28) (pK_i 7.5) 21	monoclonal antibody 3G12 17, [Ser11](N-CNP,C-ANP)pBNP2-15 16	M372049 19, AP811 (pK_i 9.3) 28	–
Radioligands (K_d)	[125I]ANP	[125I]CNP (human)	[125I]ANP	[125I]Sta

Nomenclature	HGNC, UniProt	Agonists	Comment
TLR1	TLR1, Q15399	–	–
TLR2	TLR2, O60603	peptidoglycan 41,45	–
TLR3	TLR3, O15455	polyIC 30	–
TLR4	TLR4, O00206	LPS 39, taxol 36	eritoran (E5564) is a lipid A analogue, which has been described as a TLR4 antagonist 35
TLR5	TLR5, O60602	flagellin 31	–
TLR6	TLR6, Q9Y2C9	–	–
TLR7	TLR7, Q9NYK1	imiquimod 33, loxoribine 32, R848 33	–
TLR8	TLR8, Q9NR97	imiquimod, R848 33	–
TLR9	TLR9, Q9NR96	CpG 34	–
TLR10	TLR10, Q9BXR5	–	–
TLR11	–, Q6R5P0	–	Found in the mouse

Nomenclature	HGNC, UniProt	Agonists	Comment
NLRC1	NOD1, Q9Y239	meso-DAP	–
NLRC2	NOD2, Q9HC29	muramyl dipeptide	–
NLRC3	NLRC3, Q7RTR2	–	–
NLRC5	NLRC5, Q86WI3	–	–
NLRX1	NLRX1, Q86UT6	–	–
CIITA	CIITA, P33076	–	–
NLRP1	NLRP1, Q9C000	muramyl dipeptide	–
NLRP2	NLRP2, Q9NX02	–	–
NLRP3	NLRP3, Q96P20	–	Multiple virus particles have been shown to act as agonists, including Sendai and influenza
NLRP4	NLRP4, Q96MN2	–	–
NLRP5	NLRP5, P59047	–	–
NLRP6	NLRP6, P59044	–	–
NLRP7	NLRP7, Q8WX94	–	–
NLRP8	NLRP8, Q86W28	–	–
NLRP9	NLRP9, Q7RTR0	–	–
NLRP10	NLRP10, Q86W26	–	–
NLRP11	NLRP11, P59045	–	–
NLRP12	NLRP12, P59046	–	–
NLRP13	NLRP13, Q86W25	–	–
NLRP14	NLRP14, Q86W24	–	–
IPAF	NLRC4, Q9NPP4	–	–
NAIP	NAIP, Q13075	–	–

Nomenclature	activin A receptor type II-like 1	activin A receptor, type I	bone morphogenetic protein receptor, type IA	activin A receptor, type IB	transforming growth factor, beta receptor 1	bone morphogenetic protein receptor, type IB	activin A receptor, type IC
Common abbreviation	ALK1	ALK2	BMPR1A	ALK4	TGFBR1	BMPR1B	ALK7
HGNC, UniProt	ACVRL1, P37023	ACVR1, Q04771	BMPR1A, P36894	ACVR1B, P36896	TGFBR1, P36897	BMPR1B, O00238	ACVR1C, Q8NER5

Nomenclature	activin A receptor, type IIA	activin A receptor, type IIB	anti-Mullerian hormone receptor, type II	bone morphogenetic protein receptor, type II (serine/threonine kinase)	transforming growth factor, beta receptor II (70/80kDa)
Common abbreviation	ActR2	ActR2B	MISR2	BMPR2	TGFBR2
HGNC, UniProt	ACVR2A, P27037	ACVR2B, Q13705	AMHR2, Q16671	BMPR2, Q13873	TGFBR2, P37173

Nomenclature	transforming growth factor, beta receptor III
Common abbreviation	TGFBR3
HGNC, UniProt	TGFBR3, Q03167

Nomenclature	Transforming growth factor β receptor	Bone morphogenetic protein receptors	Growth/differentiation factor receptors	Activin receptors	Anti-Müllerian hormone receptors
Subunits	transforming growth factor, beta receptor 1 (Type I), transforming growth factor, beta receptor II (70/80kDa) (Type II), transforming growth factor, beta receptor III (Type III)	activin A receptor type II-like 1 (Type I), activin A receptor, type I (Type I), bone morphogenetic protein receptor, type IA (Type I), bone morphogenetic protein receptor, type IB (Type I), activin A receptor, type IIA (Type II), activin A receptor, type IIB (Type II), bone morphogenetic protein receptor, type II (serine/threonine kinase) (Type II)	bone morphogenetic protein receptor, type IA (Type I), activin A receptor, type IB (Type I), transforming growth factor, beta receptor 1 (Type I), bone morphogenetic protein receptor, type IB (Type I), activin A receptor, type IC (Type I), activin A receptor, type IIA (Type II), activin A receptor, type IIB (Type II), bone morphogenetic protein receptor, type II (serine/threonine kinase) (Type II)	activin A receptor, type IB (Type I), activin A receptor, type IC (Type I), activin A receptor, type IIA (Type II), activin A receptor, type IIB (Type II)	activin A receptor, type I (Type I), bone morphogenetic protein receptor, type IA (Type I), bone morphogenetic protein receptor, type IB (Type I), anti-Mullerian hormone receptor, type II (Type II)
Coupling	Smad2, Smad3 48,49	Smad1, Smad5, Smad8 48,49	Smad1, Smad5, Smad8 48,49	Smad2, Smad3 49	Smad1, Smad5, Smad8 48,49
Endogenous agonists	TGFβ1 (TGFB1, P01137), TGFβ2 (TGFB2, P61812), TGFβ3 (TGFB3, P10600)	BMP-10 (BMP10, O95393), BMP-2 (BMP2, P12643), BMP-4 (BMP4, P12644), BMP-5 (BMP5, P22003), BMP-6 (BMP6, P22004), BMP-7 (BMP7, P18075), BMP-8A (BMP8A, Q7Z5Y6), BMP-8B (BMP8B, P34820), BMP-9 (GDF2, Q9UK05)	GDF1 (GDF1, P27539), GDF10 (GDF10, P55107), GDF9 (GDF9, O60383), GDF3 (GDF3, Q9NR23)	inhibin βA (INHBA, P08476), inhibin βB (INHBB, P09529)	Müllerian inhibiting substance (AMH, P03971)

Nomenclature	HGNC, UniProt	Other names
Smad1	SMAD1, Q15797	JV4-1, MADH1, MADR1
Smad2	SMAD2, Q15796	JV18-1, MADH2, MADR2
Smad3	SMAD3, P84022	HsT17436, JV15-2, MADH3
Smad4	SMAD4, Q13485	DPC4, MADH4
Smad5	SMAD5, Q99717	Dwfc, JV5-1, MADH5
Smad6	SMAD6, O43541	HsT17432, MADH6, MADH7
Smad7	SMAD7, O15105	MADH7, MADH8
Smad8	SMAD9, O15198	MADH6, MADH9

Nomenclature	Common abbreviation	HGNC, UniProt	Endogenous ligands
epidermal growth factor receptor	EGFR	EGFR, P00533	amphiregulin (AREG, AREGB, P15514), betacellulin (BTC, P35070), EGF (EGF, P01133), epigen (EPGN, Q6UW88), epiregulin (EREG, O14944), HB-EGF (HBEGF, Q99075), TGFα (TGFA, P01135)
v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3	HER3	ERBB3, P21860	NRG-1 (NRG1, Q02297), NRG-2 (NRG2, O14511)
v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4	HER4	ERBB4, Q15303	betacellulin (BTC, P35070), epiregulin (EREG, O14944), HB-EGF (HBEGF, Q99075), NRG-1 (NRG1, Q02297), NRG-2 (NRG2, O14511), NRG-3 (NRG3, P56975), NRG-4 (NRG4, Q8WWG1)

Nomenclature	Insulin receptor	Insulin-like growth factor I	Insulin receptor-related receptor
Common abbreviation	InsR	IGF1R	IRR
HGNC, UniProt	INSR, P06213	IGF1R, P08069	INSRR, P14616
Endogenous ligands	insulin (INS, P01308)	IGF1 (IGF1, P05019), IGF2 (IGF2, P01344)	–

Nomenclature	platelet-derived growth factor receptor, alpha polypeptide	platelet-derived growth factor receptor, beta polypeptide	v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog	colony stimulating factor 1 receptor	fms-related tyrosine kinase 3
Common abbreviation	PDGFRα	PDGFRβ	Kit	CSFR	FLT3
HGNC, UniProt	PDGFRA, P16234	PDGFRB, P09619	KIT, P10721	CSF1R, P07333	FLT3, P36888
Endogenous ligands	PDGF	PDGF	SCF (KITLG, P21583)	G-CSF (CSF3, P09919), GM-CSF (CSF2, P04141), M-CSF (CSF1, P09603)	FLT3L (FLT3LG, P49771)
Comment	–	–	–	–	5'-fluoroindirubinoxime has been described as a selective FLT3 inhibitor 57

Nomenclature	fms-related tyrosine kinase 1	kinase insert domain receptor (a type III receptor tyrosine kinase)	fms-related tyrosine kinase 4
Common abbreviation	VEGFR-1	VEGFR-2	VEGFR-3
HGNC, UniProt	FLT1, P17948	KDR, P35968	FLT4, P35916
Endogenous ligands	VEGFA (VEGFA, P15692), VEGFB (VEGFB, P49765)	VEGFA (VEGFA, P15692), VEGFC (VEGFC, P49767), VEGFE (PDGFC, Q9NRA1)	VEGFC (VEGFC, P49767), VEGFD (FIGF, O43915), VEGFE (PDGFC, Q9NRA1)

Nomenclature	fibroblast growth factor receptor 1	fibroblast growth factor receptor 2	fibroblast growth factor receptor 3	fibroblast growth factor receptor 4
Common abbreviation	FGFR1	FGFR2	FGFR3	FGFR4
HGNC, UniProt	FGFR1, P11362	FGFR2, P21802	FGFR3, P22607	FGFR4, P22455
Endogenous ligands	FGF-1 (FGF1, P05230), FGF-2 (FGF2, P09038), FGF-4 (FGF4, P08620) > FGF-5 (FGF5, P12034), FGF-6 (FGF6, P10767) 77	FGF-1 (FGF1, P05230) > FGF-4 (FGF4, P08620), FGF-7 (FGF7, P21781), FGF-9 (FGF9, P31371) > FGF-2 (FGF2, P09038), FGF-6 (FGF6, P10767) 77	FGF-1 (FGF1, P05230), FGF-2 (FGF2, P09038), FGF-9 (FGF9, P31371) > FGF-4 (FGF4, P08620), FGF-8 (FGF8, P55075) 77	FGF-1 (FGF1, P05230), FGF-2 (FGF2, P09038), FGF-4 (FGF4, P08620), FGF-9 (FGF9, P31371) > FGF-6 (FGF6, P10767), FGF-8 (FGF8, P55075) 77

Nomenclature	neurotrophic tyrosine kinase, receptor, type 1	neurotrophic tyrosine kinase, receptor, type 2	neurotrophic tyrosine kinase, receptor, type 3
Common abbreviation	trkA	trkB	trkC
HGNC, UniProt	NTRK1, P04629	NTRK2, Q16620	NTRK3, Q16288
Endogenous ligands	NGF (NGF, P01138) > NT-3 (NTF3, P20783)	BDNF (BDNF, P23560), NT-4 (NTF4, P34130) > NT-3 (NTF3, P20783)	NT-3 (NTF3, P20783)

Nomenclature	receptor tyrosine kinase-like orphan receptor 1	receptor tyrosine kinase-like orphan receptor 2
Common abbreviation	ROR1	ROR2
HGNC, UniProt	ROR1, Q01973	ROR2, Q01974

Nomenclature	met proto-oncogene	macrophage stimulating 1 receptor (c-met-related tyrosine kinase)
Common abbreviation	Met	Ron
HGNC, UniProt	MET, P08581	MST1R, Q04912
Endogenous ligands	HGF (HGF, P14210)	MST1 (MST1, P09603)

Nomenclature	AXL receptor tyrosine kinase	TYRO3 protein tyrosine kinase	c-mer proto-oncogene tyrosine kinase
Common abbreviation	Axl	Tyro3	Mer
HGNC, UniProt	AXL, P30530	TYRO3, Q06418	MERTK, Q12866
Endogenous ligands	Gas6 (GAS6, Q14393) 75, protein S (PROS1, P07225) 81	Gas6 (GAS6, Q14393) 75, protein S (PROS1, P07225) 81	Gas6 (GAS6, Q14393) 75

Nomenclature	tyrosine kinase with immunoglobulin-like and EGF-like domains 1	TEK tyrosine kinase, endothelial
Common abbreviation	TIE1	TIE2
HGNC, UniProt	TIE1, P35590	TEK, Q02763
Endogenous ligands	–	angiopoietin-1 (ANGPT1, Q15389), angiopoietin-4 (ANGPT4, Q9Y264)

Nomenclature

EPH receptor A1

EPH receptor A2

EPH receptor A3

EPH receptor A4

EPH receptor A5

EPH receptor A6

EPH receptor A7

EPH receptor A8

EPH receptor A10

EPH receptor B1

EPH receptor B2

EPH receptor B3

EPH receptor B4

EPH receptor B6

Common abbreviation

EphA1

EphA2

EphA3

EphA4

EphA5

EphA6

EphA7

EphA8

EphA10

EphB1

EphB2

EphB3

EphB4

EphB6

HGNC, UniProt

EPHA1, P21709

EPHA2, P29317

EPHA3, P29320

EPHA4, P54764

EPHA5, P54756

EPHA6, Q9UF33

EPHA7, Q15375

EPHA8, P29322

EPHA10, Q5JZY3

EPHB1, P54762

EPHB2, P29323

EPHB3, P54753

EPHB4, P54760

EPHB6, O15197

Nomenclature	discoidin domain receptor tyrosine kinase 1	discoidin domain receptor tyrosine kinase 2
Common abbreviation	DDR1	DDR2
HGNC, UniProt	DDR1, Q08345	DDR2, Q16832

Nomenclature	leukocyte receptor tyrosine kinase	anaplastic lymphoma receptor tyrosine kinase
Common abbreviation	LTK	ALK
HGNC, UniProt	LTK, P29376	ALK, Q9UM73
Comment	–	crizotinib appears to be a selective ALK inhibitor acting on the tyrosine kinase activity 64

Nomenclature	HGNC, UniProt	Putative endogenous ligands
RTP Type A	PTPRA, P18433	–
RTP Type B	PTPRB, P23467	–
RTP Type C	PTPRC, P08575	galectin-1 (LGALS1, P09382) 93
RTP Type D	PTPRD, P23468	netrin-G3 ligand (LRRC4B, Q9NT99) 90
RTP Type E	PTPRE, P23469	–
RTP Type F	PTPRF, P10586	netrin-G3 ligand (LRRC4B, Q9NT99) 90
RTP Type G	PTPRG, P23470	contactin-3 (CNTN3, Q9P232), contactin-4 (CNTN4, Q8IWV2), contactin-5 (CNTN5, O94779), contactin-6 (CNTN6, Q9UQ52) 88
RTP Type H	PTPRH, Q9HD43	–
RTP Type J	PTPRJ, Q12913	–
RTP Type K	PTPRK, Q15262	galectin-3 (LGALS3, P17931), galectin-3 binding protein (LGALS3BP, Q08380) 89
RTP Type M	PTPRM, P28827	–
RTP Type N	PTPRN, Q16849	–
RTP Type N2	PTPRN2, Q92932	–
RTP Type O	PTPRO, Q16827	–
RTP Type Q	PTPRQ, Q9UMZ3	–
RTP Type R	PTPRR, Q15256	–
RTP Type S	PTPRS, Q13332	chondroitin sulphate proteoglycan 3 (NCAN, O14594), netrin-G3 ligand (LRRC4B, Q9NT99) 90,92
RTP Type T	PTPRT, O14522	–
RTP Type U	PTPRU, Q92729	–
RTP Type Z1	PTPRZ1, P23471	contactin-1 (CNTN1, Q12860), pleiotrophin (PTN, C9JR52) (acts as a negative regulator) 88,91

Nomenclature	Systematic nomenclature	Common abbreviation	HGNC, UniProt	Adaptor proteins	Endogenous ligands	Comment
tumor necrosis factor receptor 1	TNFRSF1A	TNFR1	TNFRSF1A, P19438	TRADD	TNFSF1 (LTA, P01374), TNF membrane form (TNF, P01375), TNF shed form (TNF, P01375)	–
tumor necrosis factor receptor 2	TNFRSF1B	TNFR2	TNFRSF1B, P20333	TRAF1, TRAF2, TRAF5	TNFSF1 (LTA, P01374), TNF membrane form (TNF, P01375)	–
lymphotoxin β receptor	TNFRSF3	–	LTBR, P36941	TRAF3, TRAF4, TRAF5	LIGHT (TNFSF14, O43557), lymphotoxin β2α1 heterotrimer (LTA, LTB, Q06643, P01374)	–
OX40	TNFRSF4	–	TNFRSF4, P43489	TRAF1, TRAF2, TRAF3, TRAF5	OX-40 ligand (TNFSF4, P23510)	–
CD40	TNFRSF5	–	CD40, P25942	TRAF1, TRAF2, TRAF3, TRAF5, TRAF6	CD40 ligand (CD40LG, P29965)	–
Fas	TNFRSF6	–	FAS, P25445	FADD	Fas ligand (FASLG, P48023)	–
CD27	TNFRSF7	–	CD27, P26842	TRAF2, SIVA	CD70 (CD70, P32970)	–
CD30	TNFRSF8	–	TNFRSF8, P28908	TRAF1, TRAF2, TRAF3, TRAF5	CD30 ligand (TNFSF8, P32971)	–
4-1BB	TNFRSF9	–	TNFRSF9, Q07011	TRAF1, TRAF2, TRAF3	4-1BB ligand (TNFSF9, P41273)	–
death receptor 4	TNFRSF10A	DR4	TNFRSF10A, O00220	FADD	TRAIL (TNFSF10, P50591)	–
death receptor 5	TNFRSF10B	DR5	TNFRSF10B, O14763	FADD	TRAIL (TNFSF10, P50591)	–
receptor activator of NF-kappa B	TNFRSF11A	RANK	TNFRSF11A, Q9Y6Q6	TRAF1, TRAF2, TRAF3, TRAF5, TRAF6	RANK ligand (TNFSF11, O14788)	–
osteoprotegerin	TNFRSF11B	OPG	TNFRSF11B, O00300	–	–	Acts as a decoy receptor for RANK ligand (TNFSF11, O14788) and possibly for TRAIL (TNFSF10, P50591)
death receptor 3	TNFRSF25	DR3	TNFRSF25, Q93038	TRADD	TL1A (TNFSF15, O95150)	–
TWEAK receptor	TNFRSF12A	–	TNFRSF12A, Q9NP84	TRAF1, TRAF2, TRAF3	TWEAK (TNFSF12, O43508)	–
TACI	TNFRSF13B	–	TNFRSF13B, O14836	TRAF2, TRAF5, TRAF6	APRIL (TNFSF13, O75888), BAFF (TNFSF13B, Q9Y275)	–
BAFF receptor	TNFRSF13C	BAFF-R	TNFRSF13C, Q96RJ3	TRAF3	BAFF (TNFSF13B, Q9Y275)	–
herpes virus entry mediator	TNFRSF14	HVEM	TNFRSF14, Q92956	TRAF2, TRAF3, TRAF5	BTLA (BTLA, Q7Z6A9), LIGHT (TNFSF14, O43557), TNFSF1 (LTA, P01374)	–
nerve growth factor receptor	TNFRSF16	–	NGFR, P08138	TRAF2, TRAF4, TRAF6	BDNF (BDNF, P23560), NT-3 (NTF3, P20783), NT-4 (NTF4, P34130), NGF (NGF, P01138)	–
B cell maturation antigen	TNFRSF17	BCMA	TNFRSF17, Q02223	TRAF1, TRAF2, TRAF3, TRAF5, TRAF6	APRIL (TNFSF13, O75888), BAFF (TNFSF13B, Q9Y275)	–
glucocorticoid-induced TNF receptor	TNFRSF18	GITR	TNFRSF18, Q9Y5U5	TRAF1, TRAF2, TRAF3, SIVA	TL6 (TNFSF18, Q9UNG2)	–
toxicity and JNK inducer	TNFRSF19	TAJ	TNFRSF19, Q9NS68	TRAF1, TRAF2, TRAF3, TRAF5	TNFSF1 (LTA, P01374)	–
RELT	TNFRSF19L	–	RELT, Q969Z4	TRAF1	–	–
death receptor 6	TNFRSF21	DR6	TNFRSF21, O75509	TRADD	–	–
ectodysplasin A2 isoform receptor	TNFRS27	–	EDA2R, Q9HAV5	TRAF1, TRAF3, TRAF6	ectodysplasin A2 (EDA, Q92838) 94	–

215 in total

Review 1. Neurotrophins: roles in neuronal development and function.

Authors: E J Huang; L F Reichardt
Journal: Annu Rev Neurosci Date: 2001 Impact factor: 12.449

2. Cutting edge: heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex.

Authors: K Ohashi; V Burkart; S Flohé; H Kolb
Journal: J Immunol Date: 2000-01-15 Impact factor: 5.422

3. Design, Synthesis and Biological Evaluation of a Series of Novel Axl Kinase Inhibitors.

Authors: Alexis Mollard; Steven L Warner; Lee T Call; Mark L Wade; Jared J Bearss; Anupam Verma; Sunil Sharma; Hariprasad Vankayalapati; David J Bearss
Journal: ACS Med Chem Lett Date: 2011-12-08 Impact factor: 4.345

4. Prevention of platelet glycoprotein IIb/IIIa activation by 3,4-methylenedioxy-beta-nitrostyrene, a novel tyrosine kinase inhibitor.

Authors: Wei-Ya Wang; Yang-Chang Wu; Chin-Chung Wu
Journal: Mol Pharmacol Date: 2006-07-12 Impact factor: 4.436

Review 5. Interleukin-15 biology and its therapeutic implications in cancer.

Authors: Jason C Steel; Thomas A Waldmann; John C Morris
Journal: Trends Pharmacol Sci Date: 2011-10-25 Impact factor: 14.819

6. The TNF superfamily in 2009: new pathways, new indications, and new drugs.

Authors: Malú G Tansey; David E Szymkowski
Journal: Drug Discov Today Date: 2009-10-28 Impact factor: 7.851

Review 7. Anticancer molecules targeting fibroblast growth factor receptors.

Authors: Guang Liang; Zhiguo Liu; Jianzhang Wu; Yuepiao Cai; Xiaokun Li
Journal: Trends Pharmacol Sci Date: 2012-08-09 Impact factor: 14.819

8. A novel small molecule met inhibitor induces apoptosis in cells transformed by the oncogenic TPR-MET tyrosine kinase.

Authors: Martin Sattler; Yuri B Pride; Patrick Ma; Jessica L Gramlich; Stephanie C Chu; Laura A Quinnan; Sheri Shirazian; Congxin Liang; Klaus Podar; James G Christensen; Ravi Salgia
Journal: Cancer Res Date: 2003-09-01 Impact factor: 12.701

9. Anantin--a peptide antagonist of the atrial natriuretic factor (ANF). II. Determination of the primary sequence by NMR on the basis of proton assignments.

Authors: D F Wyss; H W Lahm; M Manneberg; A M Labhardt
Journal: J Antibiot (Tokyo) Date: 1991-02 Impact factor: 2.649

Review 10. Pharmacology and therapeutic potential of interferons.

Authors: Peter M George; Rekha Badiger; William Alazawi; Graham R Foster; Jane A Mitchell
Journal: Pharmacol Ther Date: 2012-03-28 Impact factor: 12.310

140 in total

1. Differential activation of human constitutive androstane receptor and its SV23 and SV24 splice variants by rilpivirine and etravirine.

Authors: Devinder Sharma; Aik Jiang Lau; Matthew A Sherman; Thomas K H Chang
Journal: Br J Pharmacol Date: 2015-02-10 Impact factor: 8.739

2. Synthesis and SAR studies of novel 6,7,8-substituted 4-substituted benzyloxyquinolin-2(1H)-one derivatives for anticancer activity.

Authors: Yi-Fong Chen; Yi-Chien Lin; Susan L Morris-Natschke; Chen-Fang Wei; Ting-Chen Shen; Hui-Yi Lin; Mei-Hua Hsu; Li-Chen Chou; Yu Zhao; Sheng-Chu Kuo; Kuo-Hsiung Lee; Li-Jiau Huang
Journal: Br J Pharmacol Date: 2015-01-13 Impact factor: 8.739

Review 3. Advances in exploring the role of microRNAs in the pathogenesis, diagnosis and therapy of cardiac diseases in China.

Authors: Z W Pan; Y J Lu; B F Yang
Journal: Br J Pharmacol Date: 2015-01-20 Impact factor: 8.739

4. High glucose-induced changes in hyaloid-retinal vessels during early ocular development of zebrafish: a short-term animal model of diabetic retinopathy.

Authors: Seung-Hyun Jung; Young Sook Kim; Yu-Ri Lee; Jin Sook Kim
Journal: Br J Pharmacol Date: 2015-11-28 Impact factor: 8.739

5. The contribution of VEGF signalling to fostamatinib-induced blood pressure elevation.

Authors: M Skinner; K Philp; D Lengel; L Coverley; E Lamm Bergström; P Glaves; H Musgrove; H Prior; M Braddock; R Huby; J O Curwen; P Duffy; A R Harmer
Journal: Br J Pharmacol Date: 2014-05 Impact factor: 8.739

6. The tyrosine kinase inhibitor bafetinib inhibits PAR2-induced activation of TRPV4 channels in vitro and pain in vivo.

Authors: M S Grace; T Lieu; B Darby; F C Abogadie; N Veldhuis; N W Bunnett; P McIntyre
Journal: Br J Pharmacol Date: 2014-08 Impact factor: 8.739

7. Toll-interacting protein contributes to mortality following myocardial infarction through promoting inflammation and apoptosis.

Authors: Nian Wan; Xiaoxiong Liu; Xiao-Jing Zhang; Yichao Zhao; Gangying Hu; Fengwei Wan; Rui Zhang; Xueyong Zhu; Hao Xia; Hongliang Li
Journal: Br J Pharmacol Date: 2015-04-24 Impact factor: 8.739

8. Pharmacological inhibition of caspase-8 limits lung tumour outgrowth.

Authors: Michela Terlizzi; Vincenzo Giuseppe Di Crescenzo; Giuseppe Perillo; Antonio Galderisi; Aldo Pinto; Rosalinda Sorrentino
Journal: Br J Pharmacol Date: 2015-06-12 Impact factor: 8.739

9. Imidazole-based alkaloid derivative LCB54-0009 suppresses ocular angiogenesis and lymphangiogenesis in models of experimental retinopathy and corneal neovascularization.

Authors: Byung-Hak Kim; Junyeop Lee; Jun-Sub Choi; Dae Young Park; Ho Young Song; Tae Kyo Park; Chung-Hyun Cho; Sang-Kyu Ye; Choun-Ki Joo; Gou Young Koh; Tae-Yoon Kim
Journal: Br J Pharmacol Date: 2015-06-26 Impact factor: 8.739

10. PPemd26, an anthraquinone derivative, suppresses angiogenesis via inhibiting VEGFR2 signalling.

Authors: S W Huang; J C Lien; S C Kuo; T F Huang
Journal: Br J Pharmacol Date: 2014-12 Impact factor: 8.739