Endoglin modulates cellular responses to TGF-beta 1

doi:10.1083/jcb.133.5.1109

This Article

	Full Text (PDF, 2090K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Lastres, P.
	Articles by Bernabeu, C.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Lastres, P.
	Articles by Bernabeu, C.


Social Bookmarking

	What's this?

ARTICLES

Endoglin modulates cellular responses to TGF-beta 1

P Lastres, A Letamendia, H Zhang, C Rius, N Almendro, U Raab, LA Lopez, C Langa, A Fabra, M Letarte and C Bernabeu
Centro de Investigaciones Biologicas, Consejo Superior de Investigaciones Cientificas (CSIC), Madrid, Spain.

Endoglin is a homodimeric membrane glycoprotein which can bind the beta 1 and beta 3 isoforms of transforming growth factor-beta (TGF-beta). We reported previously that endoglin is upregulated during monocyte differentiation. We have now observed that TGF-beta itself can stimulate the expression of endoglin in cultured human monocytes and in the U-937 monocytic line. To study the functional role of endoglin, stable transfectants of U-937 cells were generated which overexpress L- or S- endoglin isoforms, differing in their cytoplasmic domain. Inhibition of cellular proliferation and downregulation of c-myc mRNA which are normally induced by TGF-beta 1 in U-937 cells were totally abrogated in L-endoglin transfectants and much reduced in the S- endoglin transfectants. Inhibition of proliferation by TGF-beta 2 was not altered in the transfectants, in agreement with the isoform specificity of endoglin. Additional responses of U-937 cells to TGF- beta 1, including stimulation of fibronectin synthesis, cellular adhesion, platelet/endothelial cell adhesion molecule 1 (PECAM-1) phosphorylation, and homotypic aggregation were also inhibited in the endoglin transfectants. However, modulation of integrin and PECAM-1 levels and stimulation of mRNA levels for TGF-beta 1 and its receptors R-I, R-II, and betaglycan occurred normally in the endoglin transfectants. No changes in total ligand binding were observed in L- endoglin transfectants relative to mock, while a 1.5-fold increase was seen in S-endoglin transfectants. The degradation rate of the ligand was the same in all transfectants. Elucidating the mechanism by which endoglin modulates several cellular responses to TGF-beta 1 without interfering with ligand binding or degradation should increase our understanding of the complex pathways which mediate the effects of this factor.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Fonsatti, E., Nicolay, H. J.M., Altomonte, M., Covre, A., Maio, M. (2009). Targeting cancer vasculature via endoglin/CD105: a novel antibody-based diagnostic and therapeutic strategy in solid tumours. Cardiovasc Res 0: cvp332v2-cvp332 [Abstract] [Full Text]
Bot, P. T.G., Hoefer, I. E., Sluijter, J. P.G., van Vliet, P., Smits, A. M., Lebrin, F., Moll, F., de Vries, J.-P., Doevendans, P., Piek, J. J., Pasterkamp, G., Goumans, M.-J. (2009). Increased Expression of the Transforming Growth Factor-{beta} Signaling Pathway, Endoglin, and Early Growth Response-1 in Stable Plaques. Stroke 40: 439-447 [Abstract] [Full Text]
Lee, N. Y., Ray, B., How, T., Blobe, G. C. (2008). Endoglin Promotes Transforming Growth Factor {beta}-mediated Smad 1/5/8 Signaling and Inhibits Endothelial Cell Migration through Its Association with GIPC. J. Biol. Chem. 283: 32527-32533 [Abstract] [Full Text]
De Paepe, M. E., Patel, C., Tsai, A., Gundavarapu, S., Mao, Q. (2008). Endoglin (CD105) Up-regulation in Pulmonary Microvasculature of Ventilated Preterm Infants. Am. J. Respir. Crit. Care Med. 178: 180-187 [Abstract] [Full Text]
Dallas, N. A., Samuel, S., Xia, L., Fan, F., Gray, M. J., Lim, S. J., Ellis, L. M. (2008). Endoglin (CD105): A Marker of Tumor Vasculature and Potential Target for Therapy. Clin. Cancer Res. 14: 1931-1937 [Abstract] [Full Text]
Velasco, S., Alvarez-Munoz, P., Pericacho, M., Dijke, P. t., Bernabeu, C., Lopez-Novoa, J. M., Rodriguez-Barbero, A. (2008). L- and S-endoglin differentially modulate TGF{beta}1 signaling mediated by ALK1 and ALK5 in L6E9 myoblasts. J. Cell Sci. 121: 913-919 [Abstract] [Full Text]
Karam, J. A., Svatek, R. S., Karakiewicz, P. I., Gallina, A., Roehrborn, C. G., Slawin, K. M., Shariat, S. F. (2008). Use of Preoperative Plasma Endoglin for Prediction of Lymph Node Metastasis in Patients with Clinically Localized Prostate Cancer. Clin. Cancer Res. 14: 1418-1422 [Abstract] [Full Text]
Albini, A., Noonan, D. M., Ferrari, N. (2007). Molecular Pathways for Cancer Angioprevention. Clin. Cancer Res. 13: 4320-4325 [Abstract] [Full Text]
Lee, N. Y., Blobe, G. C. (2007). The Interaction of Endoglin with beta-Arrestin2 Regulates Transforming Growth Factor-beta-mediated ERK Activation and Migration in Endothelial Cells. J. Biol. Chem. 282: 21507-21517 [Abstract] [Full Text]
Meng, Q., Lux, A., Holloschi, A., Li, J., Hughes, J. M. X., Foerg, T., McCarthy, J. E. G., Heagerty, A. M., Kioschis, P., Hafner, M., Garland, J. M. (2006). Identification of Tctex2beta, a Novel Dynein Light Chain Family Member That Interacts with Different Transforming Growth Factor-beta Receptors. J. Biol. Chem. 281: 37069-37080 [Abstract] [Full Text]
Docherty, N. G., Lopez-Novoa, J. M., Arevalo, M., Duwel, A., Rodriguez-Pena, A., Perez-Barriocanal, F., Bernabeu, C., Eleno, N. (2006). Endoglin regulates renal ischaemia-reperfusion injury. Nephrol Dial Transplant 21: 2106-2119 [Abstract] [Full Text]
Pece-Barbara, N., Vera, S., Kathirkamathamby, K., Liebner, S., Di Guglielmo, G. M., Dejana, E., Wrana, J. L., Letarte, M. (2005). Endoglin Null Endothelial Cells Proliferate Faster and Are More Responsive to Transforming Growth Factor {beta}1 with Higher Affinity Receptors and an Activated Alk1 Pathway. J. Biol. Chem. 280: 27800-27808 [Abstract] [Full Text]
Schmidt-Weber, C. B., Letarte, M., Kunzmann, S., Ruckert, B., Bernabeu, C., Blaser, K. (2005). TGF-{beta} signaling of human T cells is modulated by the ancillary TGF-{beta} receptor endoglin. Int Immunol 17: 921-930 [Abstract] [Full Text]
Toporsian, M., Gros, R., Kabir, M. G., Vera, S., Govindaraju, K., Eidelman, D. H., Husain, M., Letarte, M. (2005). A Role for Endoglin in Coupling eNOS Activity and Regulating Vascular Tone Revealed in Hereditary Hemorrhagic Telangiectasia. Circ. Res. 96: 684-692 [Abstract] [Full Text]
Elliott, R. L., Blobe, G. C. (2005). Role of Transforming Growth Factor Beta in Human Cancer. JCO 23: 2078-2093 [Abstract] [Full Text]
Tang, H., Low, B., Rutherford, S. A., Hao, Q. (2005). Thrombin induces endocytosis of endoglin and type-II TGF-{beta} receptor and down-regulation of TGF-{beta} signaling in endothelial cells. Blood 105: 1977-1985 [Abstract] [Full Text]
Lebrin, F., Deckers, M., Bertolino, P., ten Dijke, P. (2005). TGF-{beta} receptor function in the endothelium. Cardiovasc Res 65: 599-608 [Abstract] [Full Text]
Meurer, S. K., Tihaa, L., Lahme, B., Gressner, A. M., Weiskirchen, R. (2005). Identification of Endoglin in Rat Hepatic Stellate Cells: NEW INSIGHTS INTO TRANSFORMING GROWTH FACTOR {beta} RECEPTOR SIGNALING. J. Biol. Chem. 280: 3078-3087 [Abstract] [Full Text]
Sanz-Rodriguez, F., Fernandez-L., A., Zarrabeitia, R., Perez-Molino, A., Ramirez, J. R., Coto, E., Bernabeu, C., Botella, L. M. (2004). Mutation Analysis in Spanish Patients with Hereditary Hemorrhagic Telangiectasia: Deficient Endoglin Up-regulation in Activated Monocytes. Clin. Chem. 50: 2003-2011 [Abstract] [Full Text]
Sanz-Rodriguez, F., Guerrero-Esteo, M., Botella, L.-M., Banville, D., Vary, C. P. H., Bernabeu, C. (2004). Endoglin Regulates Cytoskeletal Organization through Binding to ZRP-1, a Member of the Lim Family of Proteins. J. Biol. Chem. 279: 32858-32868 [Abstract] [Full Text]
Guo, B., Kumar, S., Li, C., Slevin, M., Kumar, P. (2004). CD105 (Endoglin), Apoptosis, and Stroke. Stroke 35: e94-e95 [Full Text]
Li, C., Issa, R., Kumar, P., Hampson, I. N., Lopez-Novoa, J. M., Bernabeu, C., Kumar, S. (2003). CD105 prevents apoptosis in hypoxic endothelial cells. J. Cell Sci. 116: 2677-2685 [Abstract] [Full Text]
DUFF, S. E., LI, C., GARLAND, J. M., KUMAR, S. (2003). CD105 is important for angiogenesis: evidence and potential applications. FASEB J. 17: 984-992 [Abstract] [Full Text]
Daoud, S. S., Munson, P. J., Reinhold, W., Young, L., Prabhu, V. V., Yu, Q., LaRose, J., Kohn, K. W., Weinstein, J. N., Pommier, Y. (2003). Impact of p53 Knockout and Topotecan Treatment on Gene Expression Profiles in Human Colon Carcinoma Cells: A Pharmacogenomic Study. Cancer Res. 63: 2782-2793 [Abstract] [Full Text]
Marchuk, D. A., Srinivasan, S., Squire, T. L., Zawistowski, J. S. (2003). Vascular morphogenesis: tales of two syndromes. Hum Mol Genet 12: R97-112 [Abstract] [Full Text]
Chang, H., Brown, C. W., Matzuk, M. M. (2002). Genetic Analysis of the Mammalian Transforming Growth Factor-{beta} Superfamily. Endocr. Rev. 23: 787-823 [Abstract] [Full Text]
Botella, L. M., Sanchez-Elsner, T., Sanz-Rodriguez, F., Kojima, S., Shimada, J., Guerrero-Esteo, M., Cooreman, M. P., Ratziu, V., Langa, C., Vary, C. P. H., Ramirez, J. R., Friedman, S., Bernabeu, C. (2002). Transcriptional activation of endoglin and transforming growth factor-beta signaling components by cooperative interaction between Sp1 and KLF6: their potential role in the response to vascular injury. Blood 100: 4001-4010 [Abstract] [Full Text]
Sanchez-Elsner, T., Botella, L. M., Velasco, B., Langa, C., Bernabeu, C. (2002). Endoglin Expression Is Regulated by Transcriptional Cooperation between the Hypoxia and Transforming Growth Factor-beta Pathways. J. Biol. Chem. 277: 43799-43808 [Abstract] [Full Text]
Welt, C., Sidis, Y., Keutmann, H., Schneyer, A. (2002). Activins, Inhibins, and Follistatins: From Endocrinology to Signaling. A Paradigm for the New Millennium. Exp. Biol. Med. 227: 724-752 [Abstract] [Full Text]
Guerrero-Esteo, M., Sanchez-Elsner, T., Letamendia, A., Bernabeu, C. (2002). Extracellular and Cytoplasmic Domains of Endoglin Interact with the Transforming Growth Factor-beta Receptors I and II. J. Biol. Chem. 277: 29197-29209 [Abstract] [Full Text]
Cho, S. K., Bourdeau, A., Letarte, M., Zuniga-Pflucker, J. C. (2001). Expression and function of CD105 during the onset of hematopoiesis from Flk1+ precursors. Blood 98: 3635-3642 [Abstract] [Full Text]
Li, D., Chen, H., Mehta, J. L. (2001). Angiotensin II via Activation of Type 1 Receptor Upregulates Expression of Endoglin in Human Coronary Artery Endothelial Cells. Hypertension 38: 1062-1067 [Abstract] [Full Text]
Paquet, M.-E., Pece-Barbara, N., Vera, S., Cymerman, U., Karabegovic, A., Shovlin, C., Letarte, M. (2001). Analysis of several endoglin mutants reveals no endogenous mature or secreted protein capable of interfering with normal endoglin function. Hum Mol Genet 10: 1347-1357 [Abstract] [Full Text]
Bourdeau, A., Faughnan, M. E., McDonald, M.-L., Paterson, A. D., Wanless, I. R., Letarte, M. (2001). Potential Role of Modifier Genes Influencing Transforming Growth Factor-{beta}1 Levels in the Development of Vascular Defects in Endoglin Heterozygous Mice with Hereditary Hemorrhagic Telangiectasia. Am. J. Pathol. 158: 2011-2020 [Abstract] [Full Text]
Matsubara, S., Bourdeau, A., terBrugge, K. G., Wallace, C., Letarte, M. (2000). Analysis of Endoglin Expression in Normal Brain Tissue and in Cerebral Arteriovenous Malformations. Stroke 31: 2653-2660 [Abstract] [Full Text]
Fortunel, N. O., Hatzfeld, A., Hatzfeld, J. A. (2000). Transforming growth factor-beta : pleiotropic role in the regulation of hematopoiesis. Blood 96: 2022-2036 [Abstract] [Full Text]
Lux, A., Gallione, C. J., Marchuk, D. A. (2000). Expression analysis of endoglin missense and truncation mutations: insights into protein structure and disease mechanisms. Hum Mol Genet 9: 745-755 [Abstract] [Full Text]
Bourdeau, A., Cymerman, U., Paquet, M.-E., Meschino, W., McKinnon, W. C., Guttmacher, A. E., Becker, L., Letarte, M. (2000). Endoglin Expression Is Reduced in Normal Vessels but Still Detectable in Arteriovenous Malformations of Patients with Hereditary Hemorrhagic Telangiectasia Type 1. Am. J. Pathol. 156: 911-923 [Abstract] [Full Text]
Evangelou, A., Jindal, S. K., Brown, T. J., Letarte, M. (2000). Down-Regulation of Transforming Growth Factor {beta} Receptors by Androgen in Ovarian Cancer Cells. Cancer Res. 60: 929-935 [Abstract] [Full Text]
LI, C., HAMPSON, I. N., HAMPSON, L., KUMAR, P., BERNABEU, C., KUMAR, S. (2000). CD105 antagonizes the inhibitory signaling of transforming growth factor {beta}1 on human vascular endothelial cells. FASEB J. 14: 55-64 [Abstract] [Full Text]
PIEK, E., HELDIN, C.-H., TEN DIJKE, P. (1999). Specificity, diversity, and regulation in TGF-{beta} superfamily signaling. FASEB J. 13: 2105-2124 [Abstract] [Full Text]
Zhao, J., Sime, P. J., Bringas, P. Jr., Gauldie, J., Warburton, D. (1999). Adenovirus-mediated decorin gene transfer prevents TGF-beta -induced inhibition of lung morphogenesis. Am. J. Physiol. Lung Cell. Mol. Physiol. 277: L412-L422 [Abstract] [Full Text]
Shovlin, C. L, Letarte, M. (1999). Rare diseases bullet 4: Hereditary haemorrhagic telangiectasia and pulmonary arteriovenous malformations: issues in clinical management and review of pathogenic mechanisms. Thorax 54: 714-729 [Full Text]
Bobik, A., Agrotis, A., Kanellakis, P., Dilley, R., Krushinsky, A., Smirnov, V., Tararak, E., Condron, M., Kostolias, G. (1999). Distinct Patterns of Transforming Growth Factor-� Isoform and Receptor Expression in Human Atherosclerotic Lesions : Colocalization Implicates TGF-� in Fibrofatty Lesion Development. Circulation 99: 2883-2891 [Abstract] [Full Text]
Lux, A., Attisano, L., Marchuk, D. A. (1999). Assignment of Transforming Growth Factor beta 1 and beta 3 and a Third New Ligand to the Type I Receptor ALK-1. J. Biol. Chem. 274: 9984-9992 [Abstract] [Full Text]
Barbara, N. P., Wrana, J. L., Letarte, M. (1999). Endoglin Is an Accessory Protein That Interacts with the Signaling Receptor Complex of Multiple Members of the Transforming Growth Factor-beta Superfamily. J. Biol. Chem. 274: 584-594 [Abstract] [Full Text]
Deng, X., Bellis, S., Yan, Z., Friedman, E. (1999). Differential Responsiveness to Autocrine and Exogenous Transforming Growth Factor (TGF) {beta}1 in Cells with Nonfunctional TGF-{beta} Receptor Type III. Cell Growth Differ. 10: 11-18 [Abstract] [Full Text]
Harris-White, M. E., Chu, T., Balverde, Z., Sigel, J. J., Flanders, K. C., Frautschy, S. A. (1998). Effects of Transforming Growth Factor-beta (Isoforms 1-3) on Amyloid-beta Deposition, Inflammation, and Cell Targeting in Organotypic Hippocampal Slice Cultures. J. Neurosci. 18: 10366-10374 [Abstract] [Full Text]
Rius, C., Smith, J. D., Almendro, N., Langa, C., Botella, L. M., Marchuk, D. A., Vary, C. P.H., Bernabeu, C. (1998). Cloning of the Promoter Region of Human Endoglin, the Target Gene for Hereditary Hemorrhagic Telangiectasia Type 1. Blood 92: 4677-4690 [Abstract] [Full Text]
Letamendia, A., Lastres, P., Botella, L. M., Raab, U., Langa, C., Velasco, B., Attisano, L., Bernabeu, C. (1998). Role of Endoglin in Cellular Responses to Transforming Growth Factor-beta . A COMPARATIVE STUDY WITH BETAGLYCAN. J. Biol. Chem. 273: 33011-33019 [Abstract] [Full Text]
Caniggia, I., Taylor, C. V., Ritchie, J. W. K., Lye, S. J., Letarte, M. (1997). Endoglin Regulates Trophoblast Differentiation along the Invasive Pathway in Human Placental Villous Explants. Endocrinology 138: 4977-4988 [Abstract] [Full Text]
Ward, M. R., Agrotis, A., Kanellakis, P., Dilley, R., Jennings, G., Bobik, A. (1997). Inhibition of Protein Tyrosine Kinases Attenuates Increases in Expression of Transforming Growth Factor-� Isoforms and Their Receptors Following Arterial Injury. Arterioscler. Thromb. Vasc. Bio. 17: 2461-2470 [Abstract] [Full Text]
Yan, Z., Deng, X., Friedman, E. (2001). Oncogenic Ki-ras Confers a More Aggressive Colon Cancer Phenotype through Modification of Transforming Growth Factor-beta Receptor III. J. Biol. Chem. 276: 1555-1563 [Abstract] [Full Text]
Botella, L. M., Sanchez-Elsner, T., Rius, C., Corbi, A., Bernabeu, C. (2001). Identification of a Critical Sp1 Site within the Endoglin Promoter and Its Involvement in the Transforming Growth Factor-beta Stimulation. J. Biol. Chem. 276: 34486-34494 [Abstract] [Full Text]
Blobe, G. C., Schiemann, W. P., Pepin, M.-C., Beauchemin, M., Moustakas, A., Lodish, H. F., O'Connor-McCourt, M. D. (2001). Functional Roles for the Cytoplasmic Domain of the Type III Transforming Growth Factor beta Receptor in Regulating Transforming Growth Factor beta Signaling. J. Biol. Chem. 276: 24627-24637 [Abstract] [Full Text]