RESUMEN
Ligand affinity chromatography separation is based on unique interaction between the target analyte and a ligand, which is coupled covalently to a resin. It is a simple, rapid, selective, and efficient purification procedure of proteins providing tens of thousands fold purification in one step. The biological activity of the isolated proteins is retained in most cases thus function is revealed concomitantly with the isolation. Prior to the completion of the genome project this method facilitated rapid and reliable cloning of the corresponding gene. Upon completion of this project, a partial protein sequence is enough for retrieving its complete mRNA and hence its complete protein sequence. This method is indispensable for the isolation of both expected (e.g. receptors) but mainly unexpected, unpredicted and very much surprising binding proteins. No other approach would yield the latter. This chapter provides examples for both the expected target proteins, isolated from rich sources of human proteins, as well as the unexpected binding proteins, found by serendipity.
Asunto(s)
Proteínas Portadoras/aislamiento & purificación , Proteínas Portadoras/metabolismo , Cromatografía de Afinidad/métodos , Receptores de Citocinas/aislamiento & purificación , Receptores de Citocinas/metabolismo , Animales , Electroforesis en Gel de Poliacrilamida , Humanos , Ligandos , Ratones , Células 3T3 NIH , Análisis de Secuencia de ADNRESUMEN
In 1976-1977, I adapted reversed-phase HPLC (RP-HPLC) to peptide and protein purification, starting with pituitary proteins and continuing with the first successful purification to homogeneity of human leukocyte interferon (IFN-alpha). Using this technology, I isolated and characterized 6-8 different leukocyte interferon subtypes, which were later identified as products of the IFN-alpha gene family. Since then, RP-HPLC became a standard procedure for isolation and analysis of proteins. The successful purification of IFN-alpha led to the development of Roferon-A, a drug used for the treatment of hairy cell leukemia, hepatitis C and a variety of other diseases. Later studies with my colleagues in Israel and abroad led to isolation and discovery of several cytokine receptors and binding proteins, including those of Type I IFNs, TNF and IL-18. The use of HPLC was indispensable in most of these studies.
Asunto(s)
Interferón-alfa/aislamiento & purificación , Animales , Cromatografía Líquida de Alta Presión , Humanos , Receptores de Citocinas/aislamiento & purificaciónRESUMEN
Our approach of isolating proteins from a rich source of human proteins by ligand-affinity-chromatography enabled rapid and efficient isolation of not only soluble receptors corresponding to cell-associated receptors, but also independent binding-proteins and associated enzymes. No other approach would yield the latter. During the early 80's we prepared the tools and the infrastructure that enabled the subsequent 20 years of achievements. Thus we described eight soluble receptors (R) and binding proteins (BP) for various cytokines including the IL-6R, IFN-gammaR, TNFRI, TNFRII, LDLR, IFN-alpha/betaR, IL-18BP and IL-32BP identified as Proteinase 3. The isolation of the soluble IFN-alpha/beta receptor led to the cloning of its long sought cell surface ligand binding counterpart. We have established the concept that soluble receptors and binding proteins are normal constituents of body fluids in healthy individuals and that the levels of these biomarkers are modulated in various pathological situations. Each of these proteins contributed to basic science, one of them serves as a basis for therapy and some others are in various stages of clinical development.
Asunto(s)
Péptidos y Proteínas de Señalización Intercelular/aislamiento & purificación , Receptores de Citocinas/aislamiento & purificación , Receptores de LDL/aislamiento & purificación , Animales , Cromatografía de Afinidad , HumanosRESUMEN
A functional IP10-scFv fusion protein retaining the antibody specificity for acidic isoferritin and chemokine function was produced at high level in Esherichia coli (E. coli). IP10-scFv gene from the recombinant plasmid pc3IP104c9 was subcloned into pET28a fused to N-terminal His-tag sequence in frame and overexpressed in E. coli BL21(DE3). With an on-column refolding procedure based on Ni-chelating chromatography, the active fusion protein was recovered efficiently from inclusion bodies with a refolding yield of approximate 45% confirmed by spectrophotometer. The activity of refolded IP10-scFv was determined through sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blotting and enzyme-linked immunosorbent assay. The results showed the fusion protein retains the specific binding activity to AIF with an affinity constant of 4.48x10(-8) M as well as the chemokine function of IP-10. The overall yield of IP10-scFv with bioactivity in E. coli flask culture was more than 40 mg/L.
Asunto(s)
Cuerpos de Inclusión/química , Cuerpos de Inclusión/genética , Pliegue de Proteína , Receptores de Citocinas/genética , Proteínas Recombinantes de Fusión/aislamiento & purificación , Animales , Especificidad de Anticuerpos , Línea Celular Tumoral , Movimiento Celular/genética , Movimiento Celular/inmunología , Cromatografía de Afinidad/métodos , Clonación Molecular , Escherichia coli/genética , Escherichia coli/metabolismo , Femenino , Humanos , Región Variable de Inmunoglobulina/genética , Ratones , Ratones Endogámicos BALB C , Receptores de Citocinas/química , Receptores de Citocinas/aislamiento & purificación , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética , Linfocitos T/inmunología , Células Tumorales CultivadasAsunto(s)
Receptores de Citocinas/genética , Receptores de Citocinas/aislamiento & purificación , Anticuerpos Monoclonales , Bioensayo , Proteínas Portadoras/genética , Proteínas Portadoras/aislamiento & purificación , Cromatografía de Afinidad , Clonación Molecular , Reactivos de Enlaces Cruzados , Electroforesis en Gel de Poliacrilamida , Humanos , Técnicas In Vitro , Ligandos , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/aislamiento & purificación , Receptores de Citocinas/inmunología , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/aislamiento & purificación , Análisis de Secuencia de Proteína , Plata , Solubilidad , Coloración y EtiquetadoAsunto(s)
Citocinas/aislamiento & purificación , Receptores de Citocinas/aislamiento & purificación , Cristalización/métodos , Citocinas/química , Humanos , Sustancias Macromoleculares , Receptores de Citocinas/química , Proteínas Recombinantes/química , Proteínas Recombinantes/aislamiento & purificaciónAsunto(s)
Citocinas/historia , Receptores de Citocinas/historia , Animales , Linfocitos B/inmunología , Citocinas/aislamiento & purificación , Citocinas/fisiología , Historia del Siglo XX , Humanos , Japón , Activación de Linfocitos , Receptores de Citocinas/aislamiento & purificación , Receptores de Citocinas/fisiología , Linfocitos T/inmunologíaRESUMEN
On antigen challenge, T-helper cells differentiate into two functionally distinct subsets, Th1 and Th2, characterized by the different effector cytokines that they secrete. Th1 cells produce interleukin (IL)-2, interferon-gamma (IFN-gamma) and lymphotoxin-beta, which mediate pro-inflammatory functions critical for the development of cell-mediated immune responses, whereas Th2 cells secrete cytokines such as IL-4, IL-5 and IL-10 that enhance humoral immunity. This process of T-helper cell differentiation is tightly regulated by cytokines. Here we report a new member of the type I cytokine receptor family, designated T-cell cytokine receptor (TCCR). When challenged in vivo with protein antigen, TCCR-deficient mice had impaired Th1 response as measured by IFN-gamma production. TCCR-deficient mice also had increased susceptibility to infection with an intracellular pathogen, Listeria monocytogenes. In addition, levels of antigen-specific immunoglobulin-gamma2a, which are dependent on Th1 cells, were markedly reduced in these mice. Our results demonstrate the existence of a new cytokine receptor involved in regulating the adaptive immune response and critical to the generation of a Th1 response.
Asunto(s)
Receptores de Citocinas/aislamiento & purificación , Células TH1/inmunología , Secuencia de Aminoácidos , Animales , Linfocitos T CD4-Positivos/inmunología , Células Cultivadas , Femenino , Marcación de Gen , Hemocianinas/inmunología , Humanos , Isotipos de Inmunoglobulinas/inmunología , Interferón gamma/biosíntesis , Leucopoyesis/fisiología , Listeria monocytogenes/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Datos de Secuencia Molecular , Receptores de Citocinas/genética , Receptores de Citocinas/inmunología , Receptores de Citocinas/metabolismo , Receptores de Interleucina , Homología de Secuencia de Aminoácido , Células TH1/citología , Distribución TisularAsunto(s)
Citocinas/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de Neoplasias/metabolismo , Animales , Apoptosis/fisiología , Humanos , Immunoblotting , Proteínas de la Membrana/química , Proteínas de la Membrana/aislamiento & purificación , Ratones , Peso Molecular , Proteínas de Neoplasias/química , Proteínas de Neoplasias/aislamiento & purificación , Receptores de Citocinas/química , Receptores de Citocinas/aislamiento & purificación , Receptores de Citocinas/metabolismo , Células Tumorales CultivadasAsunto(s)
Quimiocinas CX3C , Quimiocinas CXC/fisiología , Proteínas de la Membrana/fisiología , Animales , Receptor 1 de Quimiocinas CX3C , Quimiocina CX3CL1 , Integrinas/fisiología , Células Asesinas Naturales/fisiología , Receptores de Citocinas/aislamiento & purificación , Receptores del VIH/aislamiento & purificaciónRESUMEN
In an attempt to generate a stable non-glycosylated cytokine receptor homology (CRH) domain (Tyr97-Ala309) of human granulocyte-colony stimulating factor (G-CSF) receptor, two free cysteines in the CRH domain were converted to serine by site-directed mutagenesis. Taking advantage of the tight regulation for the expression of T7 RNA polymerase, the mutated CRH domain was successfully expressed in Escherichia coli (E. coli) with a pelB signal sequence at its NH2-terminus and with a His tag at its COOH-terminus. The processed and secreted CRH domain after solubilization and in vitro refolding retained G-CSF binding activity, and its yield (approximately 40 micrograms/30 ml culture) was more than 100-fold higher than that of the mouse CRH domain expressed by the MalE fusion system in E. coli.
Asunto(s)
Receptores de Factor Estimulante de Colonias de Granulocito/biosíntesis , Secuencia de Aminoácidos , Animales , Sitios de Unión , Escherichia coli/metabolismo , Expresión Génica , Humanos , Ratones , Datos de Secuencia Molecular , Receptores de Citocinas/biosíntesis , Receptores de Citocinas/genética , Receptores de Citocinas/aislamiento & purificación , Receptores de Factor Estimulante de Colonias de Granulocito/genética , Receptores de Factor Estimulante de Colonias de Granulocito/aislamiento & purificación , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/aislamiento & purificaciónRESUMEN
We have developed a cloning vector for the expression of type I cytokine receptor, NO, extracellular domain (ECD)-mouse IgG1 Fc fusion proteins. The vector has a versatile polylinker that allows in-frame cloning of the receptor ECD with the mouse IgG1 sequence to encode a receptor ECD-IgG1 fusion construct. The receptor-IgG1 fusion proteins are transiently expressed in useful amounts following transfection of the expression vector into COS7 cells and G418 selection. The mouse IgG1 portion of the fusion protein provides a universal handle for purification on an affinity matrix and detection by anti-mouse IgG antibodies in ELISA or Western blot formats. The expressed receptor ECD-IgG1 fusion proteins bind their cognate ligands. In order to demonstrate that the fusion proteins have similar ligand binding affinities as the native receptors, the affinity constants (Kd) for EPOR, TNFR, IL-4R, and IL-6R-IgG1 fusion proteins were measured by surface plasmon resonance and shown to be in good agreement with published values. The TNFR-IgG1 fusion protein was employed in a demonstration of a novel ELISA format for detecting cytokine receptor binding to cytokine.
Asunto(s)
Inmunoglobulina G/genética , Receptores de Citocinas/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Técnicas Biosensibles , Células COS , Cartilla de ADN/genética , Expresión Génica , Vectores Genéticos , Humanos , Fragmentos Fc de Inmunoglobulinas/genética , Fragmentos Fc de Inmunoglobulinas/aislamiento & purificación , Fragmentos Fc de Inmunoglobulinas/metabolismo , Inmunoglobulina G/aislamiento & purificación , Inmunoglobulina G/metabolismo , Técnicas In Vitro , Cinética , Ligandos , Ratones , Datos de Secuencia Molecular , Receptores de Citocinas/aislamiento & purificación , Receptores de Citocinas/metabolismo , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/aislamiento & purificación , Proteínas Recombinantes de Fusión/metabolismo , TransfecciónRESUMEN
We compared the urinary concentrations of soluble TNF-I (sTNF-RI), TNF-II receptors, and soluble IL-6 receptor (sIL-6R) standardized to urinary creatinine concentrations, in children with acute pyelonephritis, in children with non-renal fever and in healthy controls. These levels were related to the acute inflammatory response in the kidneys and later renal scarring, as determined by acute and 1-y follow-up with 99mTC-dimercaptosuccinic acid scintigraphy (DMSA). The concentrations of the soluble receptors were measured using enzyme immunoassay (EIA). The urinary levels of sTNF-RI were significantly higher in children with acute pyelonephritis (median 1320 pg/mmol) than in children with non-renal fever, children 6 weeks after acute pyelonephritis and healthy controls (873, 251 and 477 pg/mumol, respectively). Median sTNF-RII urine levels were also higher in acute pyelonephritis (4123 pg/mumol) than in the three control groups (2000, 964 and 1850 pg/mumol, respectively). In contrast, the highest urinary sIL-6R concentrations were found in healthy children (median 420 pg/mumol), compared to those with acute pyelonephritis (235 pg/mumol), children with non-renal fever and children 6 weeks after pyelonephritis (137 and 50 pg/mumol, respectively). No significant difference was found in any of the urinary soluble receptor levels in children with or without DMSA uptake defects at the acute or the 1-y follow-up scintigraphy. In conclusion, although the urinary soluble TNF receptor levels were higher during acute pyelonephritis, this observation was not useful for deciding which children needed follow-up after acute pyelonephritis.
Asunto(s)
Interleucina-6/orina , Pielonefritis/orina , Receptores de Citocinas/aislamiento & purificación , Factor de Necrosis Tumoral alfa/orina , Enfermedad Aguda , Preescolar , Humanos , Lactante , Pielonefritis/inmunología , Valores de Referencia , SolubilidadRESUMEN
We describe the cloning of a human gene, named ChemR1, encoding a new putative chemokine receptor sharing 48% identity with CC-chemokine receptor (CCR)4 and 44% identity with CCR1. It displays four extracellular cysteines that are conserved among all other chemokine receptors. ChemR1 transcripts were detected by Northern blotting in the T lymphoblastic cell lines Jurkat and MOLT-4, but not in the pre-B lymphoblastic cell line JM-1. ChemR1 receptor transcripts were also detected by reverse transcription and polymerase chain reaction analysis in unstimulated CD4+ and CD8+ T cells and polymorphonuclear cells prepared from peripheral blood. The chromosomal localization was performed by radiation hybrid mapping and testing of a panel of yeast artificial chromosome clones. This allowed the assignment of the ChemR1 receptor gene to the p21.3-24 region of human chromosome 3, in close proximity with the functionally characterized CCR. Future work is required to identify the ligand(s) of this new chemokine receptor and to define its role in the recruitment of white blood cell populations.
Asunto(s)
Mapeo Cromosómico , Expresión Génica/inmunología , Neutrófilos/metabolismo , Receptores de Quimiocina , Receptores de Citocinas/genética , Linfocitos T/metabolismo , Secuencia de Aminoácidos , Secuencia de Bases , Cromosomas Humanos Par 3/inmunología , Clonación Molecular , Humanos , Datos de Secuencia Molecular , Receptores CCR8 , Receptores de Citocinas/química , Receptores de Citocinas/aislamiento & purificaciónRESUMEN
Expression and purification of the extracellular portion of granulocyte colony-stimulating factor (G-CSF) receptor, which contains an immunoglobulin-like (Ig) domain and the cytokine receptor homologous (CRH) region, using a baculovirus secretion system have shown that a tetrameric Ig-CRH protein (about 200 kDa) existed in addition to the dimer (85 kDa) [7]. Scatchard analysis revealed that the tetramer had ligand binding affinity, with a dissociation constant of about 2.5 nM. The tetramer dissociated into monomers at pH 2 and was re-formed at pH7, in contrast, the dimer was re-dimerized with the same treatment. These observations led us to hypothesize the existence of conformational heterogeneity, which leads to tetramer as well as dimer formation, in the soluble state of the Ig-CRH protein.
Asunto(s)
Receptores de Citocinas/metabolismo , Receptores de Factor Estimulante de Colonias de Granulocito/química , Receptores de Factor Estimulante de Colonias de Granulocito/metabolismo , Homología de Secuencia de Aminoácido , Inmunoglobulinas/química , Técnicas In Vitro , Unión Proteica , Conformación Proteica , Receptores de Citocinas/aislamiento & purificaciónRESUMEN
Herpesvirus Saimiri gene 13 (HVS13) exhibits 57% identity with the predicted sequence of a T cell-derived molecule termed CTLA8. Recombinant HVS13 and CTLA8 stimulate transcriptional factor NF-kappa B activity and interleukin-6 (IL-6) secretion in fibroblasts, and costimulate T cell proliferation. An HVS13.Fc fusion protein was used to isolate a cDNA encoding a novel receptor that also binds CTLA8. This receptor is unrelated to previously identified cytokine receptor families. A recombinant soluble receptor inhibited T cell proliferation and IL-2 production induced by PHA, concanavalin A (conA), and anti-TCR MAb. These results define CTLA8 and HVS13 as novel cytokines that bind to a novel cytokine receptor. We propose to call these molecules IL-17, vIL-17, and IL-17R, respectively.
Asunto(s)
Herpesvirus Saimiriino 2/inmunología , Interleucinas/aislamiento & purificación , Receptores de Citocinas/aislamiento & purificación , Receptores Inmunológicos/aislamiento & purificación , Linfocitos T/inmunología , Secuencia de Aminoácidos , Animales , Antígenos Virales/inmunología , Antígenos Virales/aislamiento & purificación , Antígenos Virales/farmacología , Secuencia de Bases , División Celular/efectos de los fármacos , Línea Celular , Clonación Molecular , Herpesvirus Saimiriino 2/genética , Interleucina-17 , Interleucinas/inmunología , Interleucinas/farmacología , Ratones , Datos de Secuencia Molecular , Receptores de Citocinas/inmunología , Receptores Inmunológicos/inmunología , Proteínas Recombinantes de Fusión/inmunologíaRESUMEN
Inflammatory bowel disease (IBD) is characterized by T-cell activation and mucosal influx of inflammatory cells partly mediated by increased local release of cytokines and chemokines. Increased levels of activated platelets are reported in IBD. Activated platelets induce endothelial cells in vitro to secrete several cytokines and growth factors and to express adhesion molecules. This study investigates the expression of interleukin-1 (IL-1), IL-8 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors on circulating platelets from patients with IBD and healthy controls and assesses the in vitro effect of various concentrations of IL-1 beta, IL-8 and GM-CSF on platelet activation in healthy controls. Flow cytometry was performed to quantify the percentage of platelets binding phycoerythrin (PE) labeled recombinant human IL-1 beta, IL-8 and GM-CSF. Platelet activation was assessed using fluorochrome labeled anti-GMP-140, an activation-dependent antigen. Results are expressed as percentage cytokine receptor expressing platelets (median and interquartile range IQR). Platelets from patients with IBD expressed significantly more cytokine receptors compared to healthy controls: IL-1R [8.7% (5.5-18.2) vs 3.1% (2.4-4.8), p < 0.05], IL-8R [22.5% (18.1-27.9) vs 8% (4.5-9.2), p < 0.001)], GM-CSFR [25.9% (16.1-39.2) vs 3.9% (2.7-3.9), p < 0.001]. The percentage of activated platelets was significantly increased after in vitro stimulation with IL-1 beta, IL-8 and GM-CSF. We conclude that cytokines and chemokines modulate platelet activation through specific, functional receptors which are upregulated in IBD.
Asunto(s)
Enfermedades Inflamatorias del Intestino/sangre , Activación Plaquetaria/efectos de los fármacos , Receptores de Citocinas/aislamiento & purificación , Plaquetas/química , Endotelio/citología , Endotelio/metabolismo , Citometría de Flujo , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Humanos , Técnicas In Vitro , Enfermedades Inflamatorias del Intestino/inmunología , Interleucina-1/farmacología , Interleucina-8/farmacología , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/aislamiento & purificación , Receptores de Interleucina/aislamiento & purificación , Receptores de Interleucina-1/aislamiento & purificación , Receptores de Interleucina-8ARESUMEN
The human erythrocyte chemokine receptor has recently been shown to be identical to the Duffy blood group antigen and is expressed in multiple organs, including kidney. Here we have examined the molecular properties of the renal isoform. Immunoblot analysis of erythrocyte and kidney detergent lysates, with a monoclonal antibody (Fy6) to the Duffy antigen, revealed that the renal isoform had a molecular mass of 43-45 kD, which could be distinguished from that observed in erythroid cells (38-47 kD). Chemical cross-linking of kidney membranes to 125I-melanoma growth stimulatory activity (MGSA) indicated that the renal chemokine receptor had a molecular mass of 38-45 kD. Binding of 125I-labeled MGSA to kidney membranes was competitively inhibited by the addition of unlabeled MGSA, IL-8, regulated on activation, normal T expressed and secrted, and monocyte chemotactic protein-1. Scatchard analysis of MGSA binding showed that the chemokine receptor from renal tissues had a binding affinity of 3.5 nM similar to that observed for the erythroid isoform (5-10 nM). The primary structure of the renal chemokine receptor predicted from the nucleotide sequence of cDNA from renal tissues is identical to that reported for the erythroid isoform. Immunocytochemical staining of kidney with Fy6 localized expression to endothelial cells present in postcapillary venules. These studies implicate the Duffy antigen/chemokine receptor in the complex interactions between postcapillary endothelial cells and granulocytes, which are modulated by pro-inflammatory chemokines.
Asunto(s)
Quimiocinas CXC , Sistema del Grupo Sanguíneo Duffy/metabolismo , Endotelio Vascular/metabolismo , Eritrocitos/metabolismo , Péptidos y Proteínas de Señalización Intercelular , Receptores de Citocinas/metabolismo , Circulación Renal , Anticuerpos Monoclonales , Unión Competitiva , Western Blotting , Membrana Celular/metabolismo , Quimiocina CXCL1 , Factores Quimiotácticos/metabolismo , Sistema del Grupo Sanguíneo Duffy/aislamiento & purificación , Membrana Eritrocítica/metabolismo , Expresión Génica , Sustancias de Crecimiento/metabolismo , Humanos , Immunoblotting , Inmunohistoquímica , Cinética , Peso Molecular , Reacción en Cadena de la Polimerasa , Receptores de Citocinas/análisis , Receptores de Citocinas/aislamiento & purificación , VénulasRESUMEN
Recently, gp130, the signal transducer for interleukin 6 (IL-6), leukemia inhibitory factor (LIF), and ciliary neurotrophice factor (CNTF), was identified as the low-affinity receptor for oncostatin M (OM). However, it is not yet clear if OM binding to gp130 requires accessory factor(s) and if gp130 alone can mediate OM signalling. Here we report that: (a) expressing murine gp130 in BAF-B03 cells (BAF-m130) resulted in the appearance of a single class of low-affinity OM binding sites; (b) chemical cross-linking studies with 125I-OM identified a 180 kDa labelled complex on BAF-m130 cells; (c) OM cross-linking to the H2981 cell line which expresses both low- and high-affinity OM receptor, identified a 180 kDa and an additional 280 kDa species; (d) 125I-OM was specifically cross-linked to soluble recombinant gp130 (sgp130-Rg) in solution; and (e) the cellular proliferation of BAF-m130 was unaffected by OM treatment. These data indicate that gp130 can act as the low-affinity receptor for OM, however, gp130-OM interactions alone are unable to elicit cellular proliferation. This suggests that an additional factor(s) are required to interact with the OM/gp130 complex to form the high-affinity functional receptor. We propose that the 280 kDa species detected on H2981 cells is likely a complex of OM, gp130, and the putative beta chain of the functional OM high-affinity receptor. Recently, OM has been shown to be the major growth factor for Kaposi's sarcoma derived cells.(ABSTRACT TRUNCATED AT 250 WORDS)