Cytokines are low molecular weight soluble proteins that are induced by immunogens, mitogens, or other stimulants to be produced by a variety of cells and have various functions such as regulation [1] and [2], hematopoiesis, cell growth, and repair of damaged tissues. Cytokines can be classified as interleukins, interferons, tumor necrosis factor superfamily, colony-stimulating factors, chemokines, growth factors, and others. Many cytokines function in the body by paracrine, autocrine or endocrine means, and have multiple, overlapping, antagonistic and synergistic physiological properties, forming a very complex cytokine regulatory network and participating in a variety of important physiological functions in the human body. (a) Classification of cytokines according to the different types of cytokine-producing cells Cytokines 1. lymphokines are mainly produced by lymphocytes, including T-lymphocytes, B-lymphocytes and NK cells. Important lymphokines are IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, IL-14, IFN-γ, TNF-β, GM-CSF and neuroleukins. 2.Monokine is mainly produced by monocytes or macrophages, such as IL-1, IL-6, IL-8, TNF-α, G-CSF and M-CSF, etc. 3. Cytokines produced by non-lymphocytes and non-monocyte-macrophages Mainly produced by stromal cells, vascular endothelial cells, fibroblasts and other cells in bone marrow and thymus, such as EPO, IL-7, IL-11, SCF, endothelium-derived IL-8 and IFN-β, etc. (ii) Classified according to the different functions of cytokines 1. interleukin (IL) Named since 1979. Cytokines produced by lymphocytes, monocytes or other non-monocytes play an important regulatory role in intercellular interactions, immune regulation, hematopoiesis and inflammatory processes. cDNA gene cloning and expression of all named interleukins have been successful, and more than 30 species have been reported (IL-1DIL-35). 2.Colony stimulating factor (CSF) is named as G (granulocyte)-CSF, M (macrophage)-CSF, GM (granulocyte, macrophage)-CSF, G (granulocyte, macrophage)-CSF and G (granulocyte, macrophage)-CSF according to different cytokines stimulating hematopoietic stem cells or hematopoietic cells in different stages of differentiation to form different cell colonies in semi-solid medium. Multi (multiple)-CSF (IL-3), SCF, EPO, etc. Different CSFs can not only stimulate the differentiation of hematopoietic stem cells and progenitor cells at different developmental stages of proliferation, but also promote the function of mature cells. 3.Interferon (IFN) is a cytokine discovered in 1957, initially found that a certain virus-infected cells can produce a substance that can interfere with the infection and replication of another virus, hence the name. Depending on the source and structure of interferon production, they can be classified as IFN-α, IFN-β and IFN-γ, which are produced by leukocytes, fibroblasts and activated T cells, respectively. The biological activities of various different IFNs are basically the same, with antiviral, antitumor and immunomodulatory effects. Cytokine 4, tumor necrosis factor (TNF) was first discovered to cause necrosis of tumor tissues and got its name from the discovery of this substance. According to its source and structure, it can be divided into two types: TNF-α, which is produced by monocytes-macrophages, and TNF-β, which is produced by activated T cells, also known as lymphotoxin (LT). The basic biological activities of the two types of TNF are similar. In addition to killing tumor cells, they are immunomodulatory and involved in the development of fever and inflammation. High doses of TNF-α can cause cachexia, thus TNF-α is also called cachectin. 5.Transforming growth factor-β family (TGF-β family) is produced by a variety of cells, mainly including TGF-β1, TGF-β2, TGF-β3, TGFβ1β2 and bone formation protein (BMP). 6, growth factor (GF) such as epidermal growth factor (EGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), hepatocyte growth factor (HGF), insulin-like growth factor-I (IGF-1), IGF-II, leukemia inhibitory factor (LIF), nerve growth factor (NGF), and Oncostatin M (OSM), platelet-derived endothelial cell growth factor (PDECGF), transforming growth factor-α (TGF-α), vascular endothelial cell growth factor (VEGF), etc. The chemokinefamily includes two subfamilies: (1) the C-X-C/α subfamily, which mainly chemotactic for neutrophils. The major members are IL-8, melanoma cell growth stimulating activity (GRO/MGSA), platelet factor-4 (PF-4), platelet basic protein, protein hydrolysis-derived products CTAP-III and β- thromboglobulin, inflammatory protein 10 (IP-10), and ENA-78; (2) the C-C/β subclade, which primarily chemotactic monocytes, members of this subclade include macrophage inflammatory protein 1α (MIP-1α), MIP-1β, RANTES, monocyte chemotactic protein-1 (MCP-1/MCAF), MCP-2 Cytokines are peptide molecules produced by a variety of cells and have a wide range of regulatory effects on cellular functions. Cytokines act not only in the immune and hematopoietic systems, but also in the neurological and endocrine systems, and have important regulatory effects on cellular interactions, cell proliferation and differentiation, and effector functions. Cytokines perform a wide variety of biological functions by binding to receptors on the surface of target cell membranes and transmitting signals to the cell interior. Therefore, understanding the structure and function of cytokine receptors is essential for an in-depth study of the biological functions of cytokines. The discovery of shared chains in different subunits of cytokine receptors has provided a basis for elucidating the similarities and differences in the biological activities of numerous cytokines from the receptor level. The vast majority of cytokine receptors exist in soluble forms, and the knowledge of the patterns of soluble cytokine receptor production and their physiological and pathological significance will certainly expand the understanding of the role of cytokine networks. The detection of cytokines and their receptor levels has become an important aspect of basic and clinical immunology research. Classification I. Structure and classification of cytokine receptors Based on the cDNA sequence of cytokine receptors and the homology and structural sign of the amino acid sequence of the extracellular membrane region of receptors, cytokine receptors can be classified into four main types: immunoglobulin superfamily (IGSF), hematopoietic cytokine receptor superfamily, nerve growth factor receptor superfamily, and chemokine receptors. In addition, there are some cytokine receptors whose structures have not been fully understood, such as IL-10R and IL-12R; some cytokine receptors whose structures have been understood but not yet categorized, such as IL-2Rα chain (CD25). (i) Immunoglobulin superfamily All members of this family have one or several immunoglobulin (Ig)-like structures in the extracellular membrane part. IL-1RtI (CD121a), IL-1RtII (CD121b), IL-6Rα chain (CD126), gp130 (CDw130), G-CSFR, M-CSFR (CD115), SCFR (CD117) and PDGFR are known to belong to the cytokine receptors of the IGSF members and can be classified into several different structural types, and the signaling pathways of receptors with different IGSF structural types differ. (1) M-CSFR, SCFR and PDGFR: The extracellular membrane region contains five Ig-like structural domains, of which one is a V-like structure close to the cell membrane region and the remaining four are C2-like structures. The receptors usually bind to the corresponding homodimeric ligands in dimeric form. The receptor cytoplasmic region itself contains a proteintyrosine kinase (PTK) structure. (2) IL-1RtI and IL-1RtII: both contain three C2-like structures in the extracellular membrane region, and serine/threonine phosphorylation in the receptor cytoplasmic region may be associated with receptor-mediated signaling. (3) IL-6Rα chain, gp130, and G-CSFR: The extracellular region of the cytosolic membrane contains a C2-like region at the N-terminal end and an erythropoietin receptor superfamily domain on each side near the cytosol, in addition to 2-4 fibronectin domains in the extracellular region of the cytosol. gp130 cytoplasmic region cooline phosphorylation is associated with signal transduction. This structural type of receptor and its corresponding ligands IL-6, OSM, LIF and G-CSF also share great similarity in amino acid sequence and molecular structure. （The haemopoietic cytokinereceptorsuperfamily, also known as the cytokinereceptorfamily, can be divided into the erythropoietin receptor superfamily (erythropoietin receptor superfamily) and the erythropoietin receptor family (erythropoietin receptor family). erythropoietinreceptorsuperfamily (ERS) and interferon receptor family (interferonreceptorfamily). All members of ERS have high homology in amino acid sequence and molecular structural similarity with erythropoietin (EPO) receptor extracellular region, hence the name. (1) Members of ERS: The members belonging to ERS are EPOR, plateletogenin R, IL-2β chain (CD122), IL-2Rγ chain, IL-3Rα chain (CD123), IL-3Rβ, IIL-4R (CDw124), IL-5Rα chain, IL-5βα chain, IL-5Rβ chain, IL-6Rα chain (CD126) gp130 (CDw123), IL-7R, IL-9R, IL-11R, IL-1240kDa subunit, G-CSFR, GM-CSFRα chain, GM=CSFRβ chain, LIFR, CNTFR, etc. In addition, certain hormones such as growth hormone receptor (GRGR) and prolactin receptor (PRLR) also belong to ERS. (2) Structural features of ERS: Erythropoietin receptor superfamily members have a livestock homology region containing about 210 amino acid residues at the extracellular membrane and ligand binding site, with the main features of ① four high and conserved cysteine residues Cysl, Cys2, Cys3, Cys4 and one conserved palladin near the N-terminal end of the homology region, with two disulfide residues between Cys1 and Cys2 and between Cys3 and Cys4 form two disulfide bonds between Cys1 and Cys2 and between Cys3 and Cys4. The homologous region near the cell membrane has a tryptophan a serine-X-tryptophan-serine motif at about amino acid group 18-22 outside the cell membrane, the so-called Trp-Ser-Xaa-Trp-Ser that is WSXWS motif, whose biological function is unknown. the IL-3α chain, IL-3Rβ chain, GM-CSFRβ chain, and LIFR office have two ERS structural domains In 1994, Hilton et al. synthesized the corresponding oligonucleotide of the WSXWS motif as a probe and successfully cloned the mouse IL-11 receptor α chain cDNA from an adult mouse liver cDNA library. The IL-6R α-strand and gp130 and G-CSFrN-terminal have an IGSF structure. il-7R near the N-terminal side has only Cys1 and Cys3 and lacks Cys2 and Cys4 and tryptophan residues compared to the other members. the IL-1240kDa subunit has the homologous structure of ERS but is non-membrane bound and is associated with another IL-12 The 35kDa subunit opens into a heterodimer via a disulfide bond. the GM-CSFrN terminus in the ERS can be viewed as consisting of two type III fibronectin, each type III fibronectin structural domain consisting of seven antiparallel β-folded strands forming a barrel structure, and the groove between the two barrel structures is a conserved region outside the ligand membrane with a clear evolutionary homology that is similar in magnitude to that among IGSF members. EPoR appears to have higher homology with other family members and may be evolutionarily dominant. the cytoplasmic region of ERS varies in length from 54 amino acid residues to 568 amino acid residues, with the exception of some homology in the cytoplasmic region between the IL-2Rβ chain and EPOR, no significant homology is seen in the cytoplasmic region of other members. none of the ERS members have PTK structures in the cytoplasmic region itself. The cytoplasmic region of IL-2Rβ chain has a native duality region associated with tyrosine kinase in the cytoplasm, and the serine-rich region is associated with the non-kinase trust pathway. the cytoplasmic region of IL-2Rγ chain has an SH2 structure and is involved in signaling. PTK and PKC in the cytoplasm may be involved in IL-4R-mediated signaling. gp130 cytoplasmic region serine-rich regions as well as cooline phosphorylation are associated with gp130-mediated signaling. In addition, tyrosine phosphorylation is associated with IL-7R, GM-CSFRβ chain, IL-3Rβ chain, and IL-5Rβ chain-mediated signaling. 2, Interferon receptor family Members belonging to this family are IFN-α/βR, IFN-γR and tissue factor (TF) (a cell membrane receptor for coagulase factor VII), whose structure is similar to that of the erythropoietin receptor family, but contains only two conserved Cys at the N terminus, with seven amino acids between the two Cys. The proximal membrane also has two conserved Cys with 20-22 amino acids spaced between the two Cys. IFN-α/βR is composed of two of the above mentioned structural domains. (iii) Nerve growth factor receptor superfamily 1. The members of NGFR superfamily belong to this family except nervegrowthfactorreceptorNGFR, not TNF-RⅠ (CD120a), TNF-RⅡ (CD120b), CD40, CD27, T-cell cDNA-41BB encoded product, rat T-cell antigen OX40 and human myeloid cell surface activation antigen Fas (CD95). 2. Structural characteristics of NGFR superfamily NGFR superfamily members have Cys-rich regions consisting of 3-6 about 40 amino acids outside their cytosolic membranes, such as NGFR, TNF-RⅠ, TNF-RⅡ with 4 structural domains, CD95 with 3 structural domains, and CD30 with 6 structural domains. All members contain six conserved Cys and one each of Tyr, Gly and Thr residues in the first N-terminal region, while other regions also contain 4-6 Cys. There is about 40-50% homology between the cytoplasmic regions of TNF-RⅠ, CD95 and CD40 molecules. (D) chemokine receptors Since the successful cloning of IL-8 gene in 1988, a family of chemokines has been formed. To date, there are at least 19 members of the chemokine family. Some of the chemokine receptors have been largely identified, and they all belong to the GTP-bindingproteincoupledreceptor, which is also known as the 7-predictedtransmembrane receptor superfamily because it has 7 membrane-penetrating regions. G protein-coupled receptors (or STRs) include a wide range of receptors, such as certain amino acid, acetylcholine, monoamine receptors, classical chemokine (C5a, fMLP, PAF) receptors, in addition to chemokine receptors. (1) Types and structures of chemokine receptors (1) Types of chemokine receptors: The types of chemokine receptors identified are IL-8RA, IL-8RB, MIP-1α/RANTEsR, NCP-1R and cytokine receptors (redbloodcellchemokinereceptors). redbloodcellchemokinereceptorRBCCKR). IL-8RA, IL-8RB and RBCCKR (Duffy antigen), which can bind to IL-8, have been categorized as the IL-8 receptor family. (2) Structure of chemokine receptors: All chemokine receptors are G protein-coupled receptors/STRs with N-terminal outside the cytosol and C-terminal inside the cytosol. 7 transmembranedomain (TMD) are α-helices, and TMDs II, IV, V, VI and VII are kinked by conserved lung endosine inside the α-helix, and each of them is composed of hydrophilic amino acids outside the cytosol and inside the cytosol. There are three one’s each composed of hydrophilic amino acids, referred to as e1-e3 (e:extracellularconnectingloops) and il-i3 (iintracellularconnectingloops). e1 and e2 form a disulfide bond between two conserved Cys, and some receptors also form a disulfide bond between the extracellular N-terminal and e3. and e3 also form a disulfide bond between them, e.g. IL-8Ra30Cys forms a disulfide bond with 277ys. Among the STR superfamily, chemokine receptors as well as classical chemokine receptors have the following characteristics: (1) their length is the shortest in the STR superfamily, about 350 amino acids, which is mainly due to the short N-terminal and C-terminal ends, and the i3 loop contains only 16-22 amino acids; (2) homology at the amino acid level is greater than 20%; (3) i3 is rich in basic amino acids and positively charged; (4) N-terminal mimic acid (5) cytoplasmic region contains multiple serine and threonine, which may be phosphorylation sites; (6) mRNAs are mostly expressed in leukocytes. 2, IL-8 receptor family IL-8R family is a general term for the different receptors in chemokine receptors that can bind IL-8, including IL-8RA, IL-8RB and RBCCKR. (1) IL-8RA: IL-8RA cDNA was successfully cloned in 1991 and was isolated from a neutrophil cDNA expression library by Holmes et al. The human IL-8RA gene is located on chromosome 2. The human IL-8RA gene is located on chromosome 2q35 and is closely linked to and highly homologous with the IL-8RB gene, probably derived from the same ancestral gene by duplication. From the cDNA, it was deduced that IL-8RA consists of 350 amino acids with five N-linked glycosylation sites. The molecular weight of the naked peptide is 40 kDa and 55-69 kDa after glycosylation, with 77% homology to IL-8RB at the amino acid level. IL-8RA binds only to the ligand IL-8 (basic, PI8, 0-8, 5), which is related to the structure of IL-8RA, and the acidic amino acid at the N-terminal end of IL-8Ra is the site of binding to IL-8, and the N-terminal Asp11 and e3 in The IL-8RA gene is expressed in a wide range of cell types, such as neutrophils, monocytes, PGA-activated T cells, monocyte-like cell lines, melanocytes, and other cells. monocyte-like cell lines, melanoma cells, synovial fibroblasts, HL60 cells and the promyeloid cell line THP-1. (2) IL-8RB: IL-8RB cDNA was first successfully cloned from HL60 cells with an inferred amino acid residue number of 335 and a potential N-linked glycosylation site. IL-8RB can bind to IL-8, GROα, GROβ, GROγ and NAP-2 in the CXC subfamily. Human IL-8RB is mainly expressed in myeloid cells, such as neutrophils, HL60, THP-1 and AML193 cells. (3) RBCCKR: This receptor binds ligands with broad specificity, also known as multi-specificreceptor, which can bind IL-8, NAP-2, GROα in CXC subfamily and MCP-1 and RANTES in CC subfamily. human RBCCKR cDNA was successfully cloned in 1993 and the gene is localized at 1q21-q25. The mature receptor molecule consists of 338 amino acids with a molecular weight of 39 kDa and has 27% and 23% homology to IL-8RB and MIP-1α/RANTESR, respectively. The extracellular region is 66 amino acids and contains 2 potential N-linked glycosylation sites and is acidic. the C-terminal cytoplasmic region is 24 amino acid residues long and RBC-CKR does not appear to be G-protein regulated and may be a non-coupled receptor for G proteins. RBCCKR is a human erythrocyte Duffy antigen (gpD) and also a receptor for the microscopic Plasmodium vivax. Duffy blood group negative individuals do not express Duffy antigen/RBCCKR despite the presence of this blood group for this reason. RBCCKR acts as a clearancereceptor to clear chemokines from the blood. This receptor binds ligands with an affinity Kd of 5 nM and normal serum IL-8 levels are at the pM level. In adult respiratory distress syndrome (ARDS) and sepsis, serum IL-8 levels can rise to 8nM, and excessive levels of IL-8 are cleared by binding to RBCCKR. chemokines such as IL-8 lose their effect on target cells when they bind to erythrocytes. RBCCKR is expressed not only on erythrocytes but also in the kidney, brain, and in the spleen, lung, and thymus. 3, receptor signaling IL-8RA and IL-8RB in the second intracellular loop (i2) immediately after the third membrane penetrating region (TMD III) has a highly conserved DRYLAIVHA sequence, which is closely related to receptor signaling, where DRY is necessary for the receptor to effectively couple G proteins, such as altering this sequence by mutation, although it does not affect the binding of the receptor to the ligand, but IL-8R binding to the ligand causes the heterotrimeric G protein bound to the receptor to break down into α and βγ subunits. α subunit activation of phospholipase C (phospholipaseCPLC) leads to an increase in intracytoplasmic inositol triphosphate (IP3) and diacylglycerol (DAG), which induce intracytoplasmic Ca pool release, respectively Ca2 and PKC activation. In addition, phosphorylation of serine and threonine residues at the IL-8RA and IL-8RBC termini may be related to signal transduction. 4. chemokine receptors and viruses Recently, it has been found that the open reading frame products of certain infectious human or primate viruses have a high homology with certain chemokine receptors, which may be related to the pathogenicity of viruses and certain biological properties possessed by viruses. (1) humancytomegalovirusHCMV: a βHerpesvirus that infects human epithelial, myeloid, and lymphoid cells. the amino acid sequences inferred from the three open reading frames of HCMV, US27, US28, and UL33, all mimic STR in molecular structure, with US28 The US28 product has about 30% homology with human MIP-1α/RANTEsR and up to 56% homology with the N-terminal end of this receptor. the US28 product binds to MIP-1α, MIP-1β, MCP-1 and RANTES in the chemokine β subfamily, but not to chemokines in the α subfamily. (2) Saimiri herpesvirus (HerpesvirussaimiriHVS):It is a γHerpesvirus that infects primate T cells. IL-8, GROα and NAP-2 can all bind to some extent. The inability of the HCMV-US28 and HVS-ECRF3 probes to hybridize to human genomic DNA suggests that herpesviruses have not only acquired a copy of the chemokine receptor gene from the host, but have also modified it. A similar phenomenon is seen with the human B lymphocyte-loving gamma herpesvirus-EBV (EBV), where EBV open reading frame BCRF1 is an IL-10 gene acquired from the host and the BCRF1 product, also known as viral IL-10 (vIL-10), mimics the anti-inflammatory and anti-proliferative effects of mammalian IL-10. Shared chains II. Shared chains in cytokine receptors Most cytokine receptors are heterodimers or multimers composed of two or more subunits, usually including a specific ligand-binding alpha chain and a beta chain involved in signaling. alpha chains constitute low-affinity receptors, and beta chains generally cannot bind cytokines alone, but are involved in high-affinity receptor formation and signaling. The application of ligand competition binding assays, functional similarity analysis and molecular cloning techniques has revealed the existence of different cytokine receptors sharing the same chain in cytokine receptors. (A) Types of cytokine receptors sharing the same chain Among many cytokines, certain cytokines have very similar effects, such as IL-3, IL-5, GM-CSF all act on the hematopoietic system and promote the proliferation of hematopoietic stem cells or directed stem cells. IL-6, IL-11, LIF, OSM all act on hepatocytes, megakaryocytes, and plasmacytoma and exert similar biological effects. IL-2, IL-4, IL-7, IL-9, and IL-13 all have a role in stimulating the proliferation of T cells or and B cells. The similarity of the above cytokine functions has been partially explained at the receptor level and is largely determined by the cytokine receptor sharing chain. Currently, it is known that the main cytokine sharing chains are gp310, GM-CSFRβ chain and IL-2Rγ chain. 1. gp130/LIFR is a 130 kDa glycoprotein named gp130 obtained from IL-6R, monoclonal antibody MT18 in myeloma cell line U266 co-precipitation. gp130, which was successfully cloned by Hibi in 1990, belongs to the hematopoietic factor receptor family. IL-6 and IL-11 both stimulate IL-6 trusted mouse plasmacytoma line T1165 proliferation, shorten the Go phase of bone marrow pluripotent stem cells in the presence of IL-3 and GM-CSF, enhance the formation of IL-3-dependent megakaryocyte colonies in humans and mice, promote specific antibody responses in vivo and in vitro, and induce the production of hepatocyte acute phase proteins. Anti-gp130 negatively interrupts the proliferation of TF1 cells induced by IL-6 and IL-11 cytokines, respectively, whereas anti-IL-5R only negatively interrupts the proliferation of TF1 induced by IL-6, indicating that IL-6 and IL-11 receptors share a common signal transduction chain. osm receptors exist as low and high affinity receptors, with the low affinity receptor, gp130, and gp130 and LIFR constitute high affinity receptors. Unlike in IL-6R and IL-11R, gp130 forms only a low-affinity receptor in OSMR and cannot transduce cytokine signals alone. The high-affinity LIF receptor consists of LIFR and gp130. OSMR competes with LIF to bind the high-affinity LIF receptor, but not the low-affinity LIF receptor. (4) The amino acid homology of IL-11Rα chain (mouse) with IL-6Rα chain and CNTFRα chain was 24% and 22%, respectively. 2, KH97/AIC2B is shared by IL-3R, IL-5R, and GM-CSFR. In hematopoiesis, IL-3 and GM-CSF both promote the formation of immature cells, mixed cells and granulocyte-macrophage colonies, activate monocytes and promote eosinophil colony formation. IL-5 also has the effect of stimulating eosinophil differentiation in addition to promoting B cell differentiation and antibody secretion. Tests using GM-CSFRβ chain cotransfected with IL-3, IL-5 and GM-CSFRα chain respectively proved that the β chain in these three cytokine high affinity receptors are AIC2B and KH97 in mouse and human respectively, and they have 56% homology. 3, IL-2 receptor γ chain In addition to IL-2R containing γ chain, IL-4R, IL-7R, IL-9R and IL-13R complexes also share IL-2R γ chain (γc). The corresponding ligands of these receptors are a group of growth factors that act primarily on T cells. Patients with X-linked severe immunodeficiency syndrome, characterized mainly by abnormal IL-2γ chains, show abnormal T-cell development with a deficiency or marked reduction in the number of T cells, suggesting that IL-2γ chains play a crucial role in the development of T cells. IL-4 and IL-7 both play a role in the development of T cells and they share a signal transduction chain, IL-2Rγ chain, to signal T-cell proliferation . In the IL-2 receptor system, the α chain constitutes the low-affinity receptor, the medium-affinity receptor consists of β and γ chains, and the high-affinity receptor consists of α, β and γ chains, of which the γ chain is equivalent to the β chain of other cytokine receptors and participates in signaling, while the αβ chain is equivalent to the α chain and mainly plays the role of recognizing and binding ligands. (B) Shared chain and cytokine receptor signaling Cytokine signaling first requires ligand binding to the receptor and inducing the formation of receptor dimer (or trimer), so that the cytoplasmic part of the dimer (or trimer) interacts with each other, thus causing different pathways of signaling. In the IL-2R system, dimerization of the β and γ chains of the receptor is necessary for signal transduction, and IL-2R lacking the cytoplasmic region of the β chain cannot transduce signals that occur as a result of IL-2 stimulation. Most of the cytokine stimulation and signal transduction are related to tyrosine kinase activation and tyrosine phosphorylation of intracellular proteins, and binding of cytokines to receptors can cause tyrosine phosphorylation of receptor components. 60 amino acid residues at the proximal membrane end of the ERS cytoplasmic region are highly conserved, and this homologous sequence plays a key role in signal transduction of IL-6, G-CSF, EPO, and IL-7 This homologous sequence plays a key role in the signal transduction of IL-6, G-CSF, EPO, and IL-7, suggesting that these receptors may utilize similar intracellular signal transduction mechanisms. 1. gp130 mediates signal transduction in the common chain of IL-6R, IL-11R, OSMR, LIFR, CNTFR. gp130 contains a serine-rich region, a nucleotide-binding region and four GTP-binding pattern regions in its cytoplasmic region of approximately 277 amino acid residues. The serine-rich region is also present in G-CSFR, IL-2Rβ, IL-4R and EPOR, and the other ERS members share significant homology. One of the fragments is conserved in all ERS members and the other fragment is present in G-CSFR, EPOR, and KH97. Mutations in either of these two short fragments will prevent gp130 from tyrosine phosphorylation and loss of signaling ability. lIFR/gp130 heterodimers are also associated with tyrosine phosphorylation gp130 cannot undergo to tyrosine phosphorylation and loss of signaling function. lIFR/gp130 heterodimers are also associated with tyrosine phosphorylation. Although most members of the hematopoietic factor receptor family do not have tyrosine kinase structural domains, they are similar to tyrosine kinase-type growth factor receptors in that growth factors cause the formation and activation of receptor tyrosine kinase dimers associated with them, whereas hematopoietic factors may be inducing dimer formation in their receptors and leading to activation of associated tyrosine kinases. Tyrosine phosphorylation of proteins of molecular weight 97/95 kDa, important in anti-gp130 signaling, has been detected in IL-6, IL-11-stimulated TF1 cells. To tyrosine phosphorylation of proteins of different molecular weights was found in different cell lines 3T3-L1, B-cell hybridoma, and myeloid leukemia lines, suggesting the existence of cell-specific tyrosine kinases and their respective specific substrates in different cell lines, which may explain the differences in the biological roles of IL-6, IL-11, LIF, CNTF, and OSM that share gp130 in different cells I . JAK2 is a non-receptor type tyrosine kinase that can be activated by a variety of cytokine stimuli such as EPO, IL-3, G-CSF, IL-6, etc. JAK2 may be a common factor in these different cytokine receptor signaling pathways, and this receptor-linked JAK2 kinase may catalyze different substrates depending on the receptor structure, resulting in JAK2 mediates a number of different biological and chemical functions. In addition, gp130 undergoes its own tyrosine phosphate whirling upon stimulation by IL-6, IL-11, CNTF, and LIF. 2. KH97/AIC2B mediates signaling within the cytosolic region of KH97/AIC2B, the signal transduction chain of IL-3, IL-5, and GM-CSF, there are also two regions necessary for generating different signals: one is a region of about 60 amino acids upstream of Glu517 near the membrane terminus, which is necessary for the induction of c-myc and pim-1; the other region is Leu623 to Ser763 a cytoplasmic region of about 140 amino acids, which is required for the activation of Ras, Raf, MAP (mitogen-activated protein kinase) for the induction of c-fos, c-jun. hGM-CSFRα, β chain without any known enzyme catalytic region, co-transfected hGM-CSFα, β chain of Ba/F3 cells with the same ground-age as C-Myc, pim-1. pim-1 levels were associated with increased prolongation of In mouse lymphocyte lines transfected with GM-CSFα and β chains induced tyrosine phosphorylation of several intracellular proteins and caused a proliferative response. α and β chains cotransfected with mouse NIH3T3 cells expressing the GM-CSFR high-affinity receptor induced rapid tyrosine phosphorylation in the cytoplasmic region of the expressed β chains and in another 40-45 kDa protein with an envelope.