Growth/Differentiation Factor-10: A New Member of the Transforming Growth Factor-β Superfamily Related to Bone Morphogenetic Protein-3

Cunningham, Nicholas; Jenkins, Nancy A.; Gilbert, Debra J.; Copeland, Neal G.; Reddi, A. Hari; Lee, S. J.

doi:10.3109/08977199509028956

Cited by 92 publications

(65 citation statements)

References 47 publications

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“…It can induce endochondral bone formation (Wozney et al, 1988). The results of Cunningham et al (1995) in previous studies in mice suggest that GDF 10 may play multiple roles in regulating cell differentiation events, including those involved in skeletal morphogenesis. GDF 10 has been discovered in rat and human femur tissue (Hino et al, , 1999.…”

Section: Discussionmentioning

confidence: 99%

“…The TGF superfamily is a group of multifunctional proteins that are regulators of cell growth and differentiation in both embryonic and adult tissues (Cunningham et al, 1995;Hino et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…Growth differentiation factor 10 (GDF 10 ) is one of the important members of the transforming growth factor (TGF) superfamily, a group of multifunctional proteins that are regulators of cell growth and differentiation in both embryonic and adult tissues (Hino et al, 2004). Previous studies in mice allowed GDF 10 mRNA detection in both neonatal and adult bone samples with higher levels being detected in calvaria than in long bone (Cunningham et al, 1995;Takao et al, 1996). These results suggest that the GDF 10 gene may play multiple roles in regulating cell differentiation events and skeletal morphogenesis.…”

Section: Introductionmentioning

confidence: 99%

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A novel polymorphism of the GDF10 gene and its association with body measurement traits in Chinese indigenous cattle

Adoligbé¹,

Liu²,

Wang³

et al. 2011

Genet. Mol. Res.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A novel polymorphism of the GDF10 gene and its association with body measurement traits in Chinese indigenous cattle

Adoligbé¹,

Liu²,

Wang³

et al. 2011

Genet. Mol. Res.

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“…GDF10 was previously identified as a TGF-β ligand related to BMP-3 (14), although there is little information on its mechanism of action. Among several TGF-β family ligands, TGF-βs and activins signal primarily through activation of Smad2 and Smad3, whereas BMPs act through Smad1 and 5 (15,16).…”

Section: Attenuation Of Sca-1 Expression Reduces Cell Growth Andmentioning

confidence: 99%

Stem cell antigen-1 enhances tumorigenicity by disruption of growth differentiation factor-10 (GDF10)–dependent TGF-β signaling

Upadhyay

Yin

Yuan

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Stem cell antigen (Sca)-1/Ly6A, a glycerophosphatidylinositollinked surface protein, was found to be associated with murine stem cell-and progenitor cell-enriched populations, and also has been linked to the capacity of tumor-initiating cells. Despite these interesting associations, this protein's functional role in these processes remains largely unknown. To identify the mechanism underlying the protein's possible role in mammary tumorigenesis, Sca-1 expression was examined in Sca-1 +/EGFP mice during carcinogenesis. Mammary tumor cells derived from these mice readily engrafted in syngeneic mice, and tumor growth was markedly inhibited on down-regulation of Sca-1 expression. The latter effect was associated with significantly elevated expression of the TGF-β ligand growth differentiation factor-10 (GDF10), which was found to selectively activate TGF-β receptor (TβRI/II)-dependent Smad3 phosphorylation. Overexpression of GDF10 attenuated tumor formation; conversely, silencing of GDF10 expression reversed these effects. Sca-1 attenuated GDF10-dependent TGF-β signaling by disrupting the heterodimerization of TβRI and TβRII receptors. These findings suggest a new functional role for Sca-1 in maintaining tumorigenicity, in part by acting as a potent suppressor of TGF-β signaling.S tem cell antigen (Sca)-1 is a member of the Ly6A superfamily of glycerophosphatidylinositol (GPI)-anchored membrane proteins (1), which is associated with murine stem and progenitor cell populations in several tissues. In the mammary gland, Sca-1-positive cells are able to reconstitute the cleared fat pad (2, 3) and give rise to alveolar and ductal structures (4). In addition to Sca-1's normal role in stem cell self-renewal, Sca-1 expression is elevated in malignant tissues, such as retinoblastomas (5), prostate tumors (6), mammary tumors (7, 8) and chronic myeloid leukemia (9), which generally reflects a more aggressive phenotype (10). Despite these associations, the role of Sca-1 in these processes remains largely unknown. To address this question, we used Sca-1 +/EGFP mice, in which EGFP is under the control of the Sca-1 locus (11), to study mammary tumorigenesis. We found that Sca-1 suppresses TGF-β signaling by inhibiting expression of the TGF-β family ligand GDF10 and binding to the type I TGF-β receptor (TβRI), thereby inhibiting ligand-induced TGF-β receptor complex formation and Smad3 phosphorylation. This study is the first to demonstrate specific functions for Sca-1 and GDF10 in tumorigenesis. ResultsSca-1 Is Increased Early in Mammary Tumorigenesis. To explore the role of Sca-1 in tumorigenesis, we induced mammary tumors in heterozygous Sca-1 +/EGFP mice (11) using medroxyprogesterone (MPA) and 7,12-dimethylbenz[a]anthracene (DMBA) (8,12,13). Cultures of primary mammary epithelial cells exhibited enhanced EGFP fluorescence coincident with increased Sca-1 expression immediately after treatment with MPA and DMBA (( Fig. S1 A and B ), suggesting that the Sca-1 locus is activated at the onset of carcinogenesis. Both Sca-1 +/EGFP a...

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“…Bone morphogenetic proteins (BMPs) and growth differentiation factors (GDFs) belong to the TGF-β superfamily (Hogan, 1996;Bhatia et al, 1999;Celeste et al, 1990;Cunningham et al, 1995;Storm et al, 1994;Dunn et al, 1997;Padgett et al, 1987). For the BMPs and GDFs only three type-I receptors and three type-II receptors have been identified, all of which are serine threonine kinases.…”

Section: Introductionmentioning

confidence: 99%

Effect of the distribution and clustering of the type I A BMP receptor(ALK3) with the type II BMP receptor on the activation of signalling pathways

Nohe

Keating

Underhill

et al. 2003

Journal of Cell Science

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Bone morphogenetic proteins (BMPs) play an important role during embryonic development, especially in chondrogenesis, osteogenesis, neurogenesis and hematopoiesis. There are over 19 BMPs known in mammalians, but only three BMP-type-I receptors and three BMP-type-II receptors are known so far to mediate these responses. Previous reports provide evidence to support that oligomerisation of BMP receptors influences the activation of the downstream BMP signalling pathways, the Smad or the p38 MAPK pathway. To further explore the importance of BMP receptor clustering in signalling, image correlation spectroscopy has been used to investigate the clustering and distribution of BMP receptors at the surface of the cell membrane. Here we demonstrate that the co-expression of the BMP-type-II receptor (BRII) influences the aggregation and the distribution of the BMP-type-Ia receptor (BRIa) in COS7 cells and in A431 cells. We also demonstrate that BMP-2 stimulation of the cells leads to a rearrangement of receptor complexes at the cell surface. Using A431 cells and limb bud-derived mesenchymal cells, we show that co-expression of the BRII and a constitutive active BRIa-ca is necessary for the activation of the Smad pathway. Importantly using a kinase-inactive BRII the rearrangement of BRIa is blocked. Together, these findings suggest that rearrangement of the receptors at the cell surface prior to forming preformed ligand independent complexes plays a critical role in activation of the Smad pathway. It also suggests further that the kinase activity of BRII is needed for signalling beyond the activation of BRIa at the GS domain.

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Growth/Differentiation Factor-10: A New Member of the Transforming Growth Factor-β Superfamily Related to Bone Morphogenetic Protein-3

Cited by 92 publications

References 47 publications

A novel polymorphism of the GDF10 gene and its association with body measurement traits in Chinese indigenous cattle

A novel polymorphism of the GDF10 gene and its association with body measurement traits in Chinese indigenous cattle

Stem cell antigen-1 enhances tumorigenicity by disruption of growth differentiation factor-10 (GDF10)–dependent TGF-β signaling

Effect of the distribution and clustering of the type I A BMP receptor(ALK3) with the type II BMP receptor on the activation of signalling pathways

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