Expression cloning and characterization of the TGF-β type III receptor

Wang, Xiaofan; Lin, Herbert Y.; Ng-Eaton, Elinor; Downward, Julian; Lodish, Harvey F.; Weinberg, Robert A.

doi:10.1016/0092-8674(91)90074-9

Cited by 603 publications

(349 citation statements)

References 52 publications

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“…TGF-b isoforms bind to the TGF-b type II receptor (TbRII), which in turn recruits and activates the TGF-b type I receptor (TbRI) (Wrana et al, 1994;Groppe et al, 2008). TGF-b1 and TGF-b3 directly bind to the extracellular domain (ECD) of TbRII, whereas efficient binding of TGF-b2 to TbRII is facilitated by betaglycan (TbRIII) (Wang et al, 1991;Lopez-Casillas et al, 1993). The activated TGF-b receptor complex then initiates signaling through both Smad-dependent and -independent pathways (Moustakas and Heldin, 2005;Schmierer and Hill, 2007).…”

Section: Introductionmentioning

confidence: 99%

Transforming growth factor-β1 is the predominant isoform required for breast cancer cell outgrowth in bone

Mourskaia

Dong

et al. 2008

Oncogene

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Transforming growth factor (TGF)-b signaling is a potent modulator of the invasive and metastatic behavior of breast cancer cells. Indeed, breast tumor responsiveness to TGF-b is important for the development of osteolytic bone metastases. However, the specific TGF-b isoforms that promote breast cancer outgrowth in bone is unknown. We demonstrate that expression of a TGF-b ligand trap, which neutralizes TGF-b1 and TGF-b3, in MDA-MB-231 breast cancer cells diminished their outgrowth in bone and reduced the severity of osteolytic lesion formation when compared with controls. We further show that a reduction or loss of TGF-b1 expression within the bone microenvironment of TGF-b1 þ /À and TGF-b1À/À mice significantly reduced the incidence of breast tumor outgrowth compared with wild-type animals. Interestingly, those tumors capable of growing within the tibiae of TGF-b1-deficient mice had upregulated expression of all three TGF-b isoforms. Finally, breast cancer cells expressing the TGF-b ligand trap showed a pronounced reduction in their ability to form osteolytic lesions when injected into the tibiae of TGF-b1 þ /À mice. Thus, our studies show that both host-and tumor-derived TGF-b expression plays a critical role during the establishment and outgrowth of breast cancer cells in bone.

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Section: Introductionmentioning

confidence: 99%

Transforming growth factor-β1 is the predominant isoform required for breast cancer cell outgrowth in bone

Mourskaia

Dong

et al. 2008

Oncogene

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“…Other groups subsequently used either PCR, with degenerate primers designed from the above receptors' kinase domains, or low stringency hybridization to clone additional activin type I1 receptor isoforms (Attisano et al, 1992;Mathews et al, 1992). The human TGF-P type I11 receptor has been cloned and shown to be a membraneanchored proteoglycan with a short cytoplasmic domain and no obvious signaling motif (Lopez-Casillas et al, 1991;Wang et al, 1991). Its role in TGF-p signal transduction remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Developmental expression of four novel serine/threonine kinase receptors homologous to the activin/transforming growth factor‐β type II receptor family

Gustafson

Hirobe

et al. 1993

Developmental Dynamics

164

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Serinekhreonine kinase transmembrane proteins are a new family of growth factor signal transducers that includes several isoforms of the activin type I1 receptor and the type I1 receptor for transforming growth factor-p. In an effort to clone the receptor for Mullerian inhibiting substance, a member of the transforming growth factor-p superfamily, oligonucleotide primers designed from conserved regions of these receptors' kinase domains were used for PCR amplification of fetal rat urogenital ridge cDNA. We isolated four novel receptors in this manner (designated Rl-R4), each of which has structural features of the previously cloned kinases, including a small extracellular ligand-binding domain, a single hydrophobic transmembrane domain, and an intracellular serinekhreonine kinase domain. In addition, each has characteristic kinase subdomains and conserved serinekhreonine kinase sequences found in this family. Northern analysis revealed mRNA expression of R1-R4 in several tissues, including fetal urogenital ridge, testis, and ovary, as well as brain and lung. In situ hybridization further localized R1 to mesenchyme of the 14.5 to 15-day fetal rat Mullerian duct and to oocytes of preantral and antral follicles, sites that are consistent with the predicted localization of Mullerian inhibiting substance receptor. In addition, R2 localized specifically to seminiferous tubules of the postnatal testis. These newest members of the activin and transforming growth factor-p type I1 receptor family should help define the molecular mechanisms by which this ligand superfamily affects cell growth and differentiation via membrane phosphorylation.

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“…In general, the type III/betaglycan receptor exhibits equal affinity for TGF-ll and TGF-f2 although type III/betaglycan subtypes having a higher affinity for TGF-32 than for TGF-31 have also been detected (Segarini et al, 1987;Mitchell and O'Connor-McCourt, 1991a;Mitchell et al, 1992). The type III/betaglycan and type II receptors have now been cloned and sequenced (Lopez-Casillas et al, 1991;Wang et al, 1991;Lin et al, 1992). In addition, affinity-labeling and affinity chromatography studies have recently demonstrated some other TGF-3 binding proteins that are distinct from the type I, II, and III/betaglycan receptors (MacKay et al, 1990(MacKay et al, , 1992Ichijo et al, 1991;MacKay and Danielpour, 1991;O'Grady et al, 1991a,b;Segarini et al, 1992; Hannah, unpublished data), including some glycolipidanchored binding proteins .…”

Section: Introductionmentioning

confidence: 99%

Characterization of transforming growth factor-beta (TGF-beta) receptors on BeWo choriocarcinoma cells including the identification of a novel 38-kDa TGF-beta binding glycoprotein.

Mitchell

Lee

O’Connor-McCourt

1992

MBoC

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Transforming growth factor-: (TGF-f) is a potential mediator of placental trophoblast functions, including differentiation, hormone production, endometrial invasion, and immunosuppression. Equilibrium binding and affinity-labeling assays were used to investigate the binding characteristics of TGF-41 and TGF-f2 on an established human choriocarcinoma trophoblastic cell line (BeWo). The equilibrium binding experiments indicated that the BeWo cells exhibited similar average affinities and total number of binding sites for TGFf1 and TGF-,32. The Kd values obtained from Scatchard analyses were -65 pM for 125I1 TGF-31 and -40 pM for 1251-TGF-fl2, with 70 000 and 85 000 sites per cell, respectively. Competitive equilibrium binding experiments indicated that TGF-f1 and TGF-32 were equipotent (apparent half maximal inhibition [IC50] -70 pM) and that all binding sites were capable of recognizing both isoforms. Affinity-labeling studies with 1251-TGF-l1 and 1251-TGF-32 and the chemical cross-linking agent bis(sulfosuccinimidyl)suberate (BS3) revealed a predominant type III/betaglycan receptor, a low level of apparently heterogeneous type I and II receptors and an additional novel 38-kDa TGF-f binding glycoprotein that was present both under reducing and nonreducing conditions on sodium dodecyl sulfatepolyacrylamide gel electrophoresis (SDS-PAGE). Affinity-labeling saturation and competition studies indicated that the type III/betaglycan component appears to have a 7-fold higher capacity for TGF-31 than for -f2 yet exhibits a 5-to 10-fold higher affinity for TGF-,B2 than for -41. The 38-kDa TGF-1 binding component, an N-linked glycoprotein, exhibits a higher affinity for TGF-,B2 than for -f1 that is strikingly similar to that of the type III/ betaglycan receptor. This 38-kDa binding protein appears to be upregulated after methotrexate-induced differentiation of the BeWo cells.

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Expression cloning and characterization of the TGF-β type III receptor

Cited by 603 publications

References 52 publications

Transforming growth factor-β1 is the predominant isoform required for breast cancer cell outgrowth in bone

Transforming growth factor-β1 is the predominant isoform required for breast cancer cell outgrowth in bone

Developmental expression of four novel serine/threonine kinase receptors homologous to the activin/transforming growth factor‐β type II receptor family

Characterization of transforming growth factor-beta (TGF-beta) receptors on BeWo choriocarcinoma cells including the identification of a novel 38-kDa TGF-beta binding glycoprotein.

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