Table 5.

Categorization of 78 “classic” cytokines and cytokine receptors identified in this study^a.

Family	Features	Cytokines	Receptors
TNF	Contain highly conserved carboxy terminal domains; can induce receptor trimerization influencing signaling pathways		TNF RI (p55), TNF RII (p75), LT-β R, Fas (CD95), TRAIL R3, CD27, TNF R21 (DR6)
γc	Receptors contain a common γchain (γc)	IL-2
IL-4 & IL-13	Bind to shared heteromultimeric receptor complexes		IL-13 Rα1
βc	Receptors contain a common βchain (βc)		IL-5 Rα, GM-CSF Rα
IL-1	A superfamily of proteins comprised of IL-1 and IL-18 members.	IL-1RA	IL-1 RI, IL-1 RII, , IL-1R AP, IL-18 BP
IGF	Share sequence homology with the insulin family of proteins	IGF1a, IGF2	IGF RII
HGF & MSP	Contain a 4-kringle domain and a pseudo-serine protease domain that lacks enzyme activity		Met
FGF	Heparin-binding polypeptides		FGF R1, FGF R2, FGF R4
Neutrophic factors	Induce signal transduction through ligand-induced dimerization and activation of trk receptors		trk B
PDGF, VEGF, PlGF	Dimeric angiogenic factors containing an 8-cysteine motif	PDGF-B, VEGF-D	PDGF Rβ, VEGF R1, VEGF R2, VEGF R3, Neuropilin-1, Neuropilin-2
EGF	Contain at least one extracellular EGF structural unit (conserved 6-cysteine motif that forms 3 disulfide bonds)		EGF R
gp130	Receptors of the IL-6 superfamily are homologous to or contain the gp130 subunit as the common signaling component	OB	Ob R, OSM R, IL-6 Rα, IL-6 Rβ (gp130), CNTF Rα
SCF, Flt-3L, M-CSF	Contain a 4-helix bundle structure in the extracellular domain and 4 conserved cysteines; receptors are tyrosine kinases	Flt-3L, M-CSF	c-kit, Flt-3, M-CSF R
MK & PTN	Products of retinoic acid-responsive genes; developmentally-regulated molecules		RPTPβ
TGF-β	Contain a highly conserved 7-cysteine domain that forms a characteristic cysteine knot	TGF-β1, TGF-β3, BMP-1, BMP-3, GDF-2, Inh β C, Inh β E	TGF-β RII, TGF-β RIII, BMPR-II, GFRα2, Act RII,
CC chemokine	Target population include: lymphoid cells (T cells and NK cells), monocytes and PMNs	HCC-1, MIP-1d , HCC-4, 6Ckine, Eot-2, CTACK,	CCR5, CCR10
CXC chemokine	Target population include: predominantly PMNs, but also T and B cells	PF4, CXCL16
Unique		IL-32, MIF	GH R, IFN-α/α Rα, IFN- α/β Rβ, IL-10 Rα, IL-10 Rβ, IL-17 R, IL-23 R, IL-31 Rα, TLR4

^aCytokine nomenclature and categorization are from http://www.rndsystems.com and Ref. 57. TNF, tumor necrosis factor; LT-β, lymphotoxin beta; TRAIL, TNF-related apoptosis-inducing ligand; DR6, death receptor 6; IL, interleukin; GM-CSF, granulocyte macrophage colony stimulating factor; IL-1RA, interleukin 1 receptor antagonist; IL-1R AP, interleukin 1 receptor accessory protein; IL-18 BP, interleukin 18 binding protein; IGF, insulin-like growth factor; HGF, hepatocyte growth factor; MSP, macrophage stimulating protein; Met, hepatocyte growth factor receptor; FGF, fibroblast growth factor; trk B, neurotrophic tyrosine kinase receptor type 2; PDGF, platelet-derived growth factor; VEGF, vascular endothelial growth factor; PlGF, placenta growth factor; EGF, epidermal growth factor; OB, leptin; OSM, oncostatin M; CNTF, ciliary neurotrophic factor; SCF, stem cell factor; Flt-3L, fms-like tyrosine kinase 3 ligand; M-CSF, macrophage-colony stimulating factor; c-kit, SCF receptor; MK, midkine; PTN, pleiotrophin; RPTPβ, receptor-type tyrosine-protein phosphatase beta; TGF, transforming growth factor; BMP, bone morphogenetic protein; GDF, growth/differentiation factor; Inh β C, inhibin beta C chain; Inh β E, inhibin beta E chain; GFR, glial-derived neurotrophic factor receptor; Act, activin; NK cells, natural killer cells; PMN, polymorphonuclear leukocytes; HCC, hemofiltrate CC (a class of chemokines); MIP, macrophage inflammatory protein; 6Ckine, 6-cysteine chemokine; Eot, eotaxin; CTACK, cutaneous T cell-attracting chemokine; CCR, CC chemokine receptor; PF4, platelet factor 4; CXCL16, CXC-chemokine ligand 16; MIF, macrophage migration inhibitory factor; GH R, growth hormone receptor; IFN, interferon; TLR, toll-like receptor.