Table V

Categorization of 78 classic cytokines and cytokine receptors identified in this study

Cytokine nomenclature and categorization are from R&D Systems and Ref. 57. LT-β, lymphotoxin beta; TRAIL, TNF-related apoptosis-inducing ligand; DR6, death receptor 6; 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; 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; 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; c-kit, stem cell factor receptor; MK, midkine; PTN, pleiotrophin; RPTPβ, receptor-type tyrosine-protein phosphatase β; BMP, bone morphogenetic protein; GDF, growth/differentiation factor; Inh β C, inhibin β C chain; Inh β E, inhibin β E chain; GFR, glia-derived neurotrophic factor receptor; Act, activin; NK cells, natural killer cells; PMNs, 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.

FamilyFeaturesCytokinesReceptors
TNFContain highly conserved carboxyl-terminal domains; can induce receptor trimerization influencing signaling pathwaysTNF RI (p55), TNF RII (p75), LT-β R, Fas (CD95), TRAIL R3, CD27, TNF R21 (DR6)
γcReceptors contain a common γ chain (γc)IL-2
IL-4 and IL-13Bind to shared heteromultimeric receptor complexesIL-13 Rα1
βcReceptors contain a common β chain (βc)IL-5 Rα, GM-CSF Rα
IL-1A superfamily of proteins comprised of IL-1 and IL-18 membersIL-1RAIL-1 RI, IL-1 RII, IL-1R AP, IL-18 BP
IGFShare sequence homology with the insulin family of proteinsIGF1a, IGF2IGF RII
HGF and MSPContain a 4-kringle domain and a pseudo-serine protease domain that lacks enzyme activityMet
FGFHeparin-binding polypeptidesFGF R1, FGF R2, FGF R4
Neurotrophic factorsInduce signal transduction through ligand-induced dimerization and activation of trk receptorstrk B
PDGF, VEGF, PlGFDimeric angiogenic factors containing an 8-cysteine motifPDGF-B, VEGF-DPDGF Rβ, VEGF R1, VEGF R2, VEGF R3, Neuropilin-1, Neuropilin-2
EGFContain at least one extracellular EGF structural unit (conserved 6-cysteine motif that forms three disulfide bonds)EGF R
Gp130Receptors of the IL-6 superfamily are homologous to or contain the gp130 subunit as the common signaling componentOBOb R, OSM R, IL-6 Rα, IL-6 Rβ (gp130), CNTF Rα
SCF, Flt-3L, M-CSFContain a 4-helix bundle structure in the extracellular domain and 4 conserved cysteines; receptors are tyrosine kinasesFlt-3L, M-CSFc-kit, Flt-3, M-CSF R
MK and PTNProducts of retinoic acid-responsive genes; developmentally regulated moleculesRPTPβ
TGF-βContain a highly conserved 7-cysteine domain that forms a characteristic cysteine knotTGF-β1, TGF-β3, BMP-1, BMP-3, GDF-2, Inh β C, Inh β ETGF-β RII, TGF-β RIII, BMPR-II, GFRα2, Act RII,
CC chemokineTarget population include: lymphoid cells (T-cells and NK cells), monocytes and PMNsHCC-1, MIP-1δ, HCC-4, 6Ckine, Eot-2, CTACK,CCR5, CCR10
CXC chemokineTarget population includes predominantly PMNs but also T- and B-cellsPF4, CXCL16
UniqueIL-32, MIFGH R, IFN-α/β Rα, IFN-α/β Rβ, IL-10 Rα, IL-10 Rβ, IL-17 R, IL-23 R, IL-31 Ra, TLR4