Research Topics
Genomes and Genes | Peter ten DijkeSummaryAffiliation: Leiden University Medical Center Country: The Netherlands Publications
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Publications
Deregulated bone morphogenetic protein receptor signaling underlies fibrodysplasia ossificans progressivaDavid J J de Gorter
Department of Molecular Cell Biology, Leiden University Medical Center, The Netherlands
Curr Pharm Des 18:4087-92. 2012..This discovery has paved the way for further investigations into the molecular basis underlying FOP and has recently pointed towards potential strategies to treat this devastating disease...
BMP-7 inhibits TGF-β-induced invasion of breast cancer cells through inhibition of integrin β(3) expressionHildegonda P H Naber
Department of Molecular Cell Biology and Centre for Biomedical Genetics, Leiden University Medical Center, Leiden, The Netherlands
Cell Oncol (Dordr) 35:19-28. 2012..In breast cancer, high levels of TGF-β are associated with poor outcome, whereas inhibition of TGF-β-signaling reduces metastasis. In contrast, BMP-7 inhibits bone metastasis of breast cancer cells...
TGF-β signaling in endothelial-to-mesenchymal transition: the role of shear stress and primary ciliaPeter Ten Dijke
Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, Netherlands
Sci Signal 5:pt2. 2012..Here, we show that shear stress activates TGF-β-Alk5 signaling in ECs, which is necessary for EndoMT in the cushions. Moreover, we show that the absence of a primary cilium is critically important for this transition process...
TGF-β signaling in breast cancer cell invasion and bone metastasisYvette Drabsch
Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands
J Mammary Gland Biol Neoplasia 16:97-108. 2011..The therapeutic strategies to target the TGF-β pathway in breast cancer are becoming increasingly clear. This review will focus on the role TGF-β in breast cancer invasion and metastasis...
TGF-β in progression of liver diseaseSteven Dooley
Molecular Hepatology Alcohol Associated Diseases II Medical Clinic Medical Faculty Mannheim, Heidelberg University, Theodor Kutzer Ufer 1 3, 68167 Mannheim, Germany
Cell Tissue Res 347:245-56. 2012..We emphasise that, in order to achieve therapeutic effects, we need to target TGF-β signalling in the right cell type at the right time...
Dual exon skipping in myostatin and dystrophin for Duchenne muscular dystrophyDwi U Kemaladewi
Center for Human and Clinical Genetics, Leiden University Medical Center, Postzone S4 P, PO Box 9600, Leiden, 2300RC, The Netherlands
BMC Med Genomics 4:36. 2011..In this study, we aim to knockdown myostatin by means of exon skipping, a technique which has been successfully applied to reframe the genetic defect of dystrophin gene in DMD patients...
Smad7 and protein phosphatase 1alpha are critical determinants in the duration of TGF-beta/ALK1 signaling in endothelial cellsGudrun Valdimarsdottir
Dept of Biochemistry and Molecular Biology, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik, Iceland
BMC Cell Biol 7:16. 2006..Besides differential receptor binding, the duration of TGF-beta signaling is an important specificity determinant for signaling responses. TGF-beta/ALK1-induced Smad1/5 phosphorylation in ECs occurs transiently...
A rapid and sensitive bioassay to measure bone morphogenetic protein activityLior Zilberberg
Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA
BMC Cell Biol 8:41. 2007..In this paper, we describe a highly sensitive, rapid, and specific cell-based assay for the quantification of BMP activity...
Endoglin in angiogenesis and vascular diseasesPeter Ten Dijke
Department of Molecular Cell Biology, Leiden University Medical Center, Building 2, Room R 02 022, Postzone S 1 P, Postbus 9600, 2300 RC, Leiden, The Netherlands
Angiogenesis 11:79-89. 2008..These exciting advances provide opportunities for the development of new therapies for diseases with vascular abnormalities...
Extracellular control of TGFbeta signalling in vascular development and diseasePeter Ten Dijke
Molecular Cell Biology, Leiden University Medical Center, Postbus 9600, 2300 RC Leiden, The Netherlands
Nat Rev Mol Cell Biol 8:857-69. 2007..Together, these extracellular interactions determine the final bioavailability of TGFbeta to vascular cells, and dysregulation is associated with an increasing number of vascular pathologies...
Elevated transforming growth factor β and mitogen-activated protein kinase pathways mediate fibrotic traits of Dupuytren's disease fibroblastsCarola Krause
Department of Molecular Cell Biology and Centre for Biomedical Genetics, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands
Fibrogenesis Tissue Repair 4:14. 2011..abstract:..
Osteocyte-derived sclerostin inhibits bone formation: its role in bone morphogenetic protein and Wnt signalingPeter Ten Dijke
Department of Molecular Cell Biology, Building 2, Room R 02 022, Leiden University Medical Center, Postzone S 1 P, PO Box 9600, 2300 RC Leiden, The Netherlands
J Bone Joint Surg Am 90:31-5. 2008..Thus, high bone mass in sclerosteosis and Van Buchem disease may result from increased Wnt signaling due to the absence of or insensitivity to sclerostin...
Bone morphogenetic protein signal transduction in boneP ten Dijke
Department of Molecular and Cell Biology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
Curr Med Res Opin 22:S7-11. 2006..Extracellular antagonists, such as noggin, inhibit binding to BMP receptors. BMP-2 and BMP-7 have demonstrated clinical utility for bone regeneration, and are commercially available through the use of recombinant DNA technology...
Smad2 and Smad3 have opposing roles in breast cancer bone metastasis by differentially affecting tumor angiogenesisM Petersen
Department of Molecular Cell Biology and Centre for Biomedical Genetics, Leiden, The Netherlands
Oncogene 29:1351-61. 2010..Thus, Smad2 and Smad3 differentially affect breast cancer bone metastasis formation in vivo...
BMP-9 signals via ALK1 and inhibits bFGF-induced endothelial cell proliferation and VEGF-stimulated angiogenesisMarion Scharpfenecker
Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands
J Cell Sci 120:964-72. 2007..Taken together, these results suggest that BMP-9 is a physiological ALK1 ligand that plays an important role in the regulation of angiogenesis...
Controlling angiogenesis by two unique TGF-β type I receptor signaling pathwaysValeria V Orlova
Department of Molecular Cell Biology, and Centre for Biomedical Genetics, Leiden University Medical Center, RC Leiden, The Netherlands
Histol Histopathol 26:1219-30. 2011..In this review, we discuss our current understanding of the TGF-β signaling pathway and its regulation of endothelial and vascular smooth muscle cell function...
Critical role of endoglin in tumor cell plasticity of Ewing sarcoma and melanomaE Pardali
Department of Molecular Cell Biology, Centre for Biomedical Genetics, Leiden University Medical Center, Leiden, The Netherlands
Oncogene 30:334-45. 2011..The present study delineates an important role of endoglin in tumor cell plasticity and progression of aggressive tumors...
Shear induced collateral artery growth modulated by endoglin but not by ALK1Leonard Seghers
Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
J Cell Mol Med 16:2440-50. 2012..Importantly, endoglin contributes to both shear induced collateral artery growth and to ischaemia induced angiogenesis, whereas ALK1 is only involved in ischaemia induced angiogenesis...
Oral administration of GW788388, an inhibitor of TGF-beta type I and II receptor kinases, decreases renal fibrosisM Petersen
Department of Molecular Cell Biology, Leiden University Medical Centre, Leiden, The Netherlands
Kidney Int 73:705-15. 2008..Our study shows that GW788388 is a potent and selective inhibitor of TGF-beta signalling in vitro and renal fibrosis in vivo...
Role of TGF-beta in the tumor stromaH P H Naber
Department of Molecular Cell Biology, Leiden University Medical Centre, Postbus 9600, 2300 RC Leiden, The Netherlands
Curr Cancer Drug Targets 8:466-72. 2008..TGF-beta can either stimulate or inhibit the tumor-promoting effects of the different components of the tumor stroma. In this review, we discuss our current understanding on how TGF-beta influences different stromal compartments...
Distinct and overlapping patterns of localization of bone morphogenetic protein (BMP) family members and a BMP type II receptor during fracture healing in ratsT Onishi
Department of Orthopaedic Surgery, Faculty of Medicine, Kagoshima University, Japan
Bone 22:605-12. 1998..Thus, these findings suggested that BMPs acting through their BMP receptors may play major roles in modulating the sequential events leading to bone formation...
Endoglin forms a heteromeric complex with the signaling receptors for transforming growth factor-betaH Yamashita
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden
J Biol Chem 269:1995-2001. 1994..These results revealed that endoglin is a phosphorylated protein which forms a heteromeric complex with signaling receptors for TGF-beta...
Efficient association of an amino-terminally extended form of human latent transforming growth factor-beta binding protein with the extracellular matrixA Olofsson
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden
J Biol Chem 270:31294-7. 1995..These results suggest that the different splice forms of LTBP-1 mediate different localization patterns of the latent TGF-beta complexes in vivo...
Enhanced expression of type I receptors for bone morphogenetic proteins during bone formationY Ishidou
Department of Orthopaedic Surgery, Faculty of Medicine, Kagoshima University, Japan
J Bone Miner Res 10:1651-9. 1995..The present data suggest that expression of BMP type I receptors is up-regulated during bone formation, and that they may play important roles in bone morphogenesis...
Bone morphogenetic protein type IB receptor is progressively expressed in malignant glioma tumoursN Yamada
Ludwig Institute for Cancer Research, Uppsala, Sweden
Br J Cancer 73:624-9. 1996..These results suggest the presence of BMP receptors and a functional role for BMPs in malignant glioma...
Latent transforming growth factor-beta complex in Chinese hamster ovary cells contains the multifunctional cysteine-rich fibroblast growth factor receptor, also termed E-selectin-ligand or MG-160A Olofsson
Ludwig Institute for Cancer Research, Box 595, Biomedical Center, S 751 24 Uppsala, Sweden
Biochem J 324:427-34. 1997....
Cartilage-derived morphogenetic proteins and osteogenic protein-1 differentially regulate osteogenesisL Erlacher
Craniofacial and Skeletal Diseases Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland, USA
J Bone Miner Res 13:383-92. 1998..Our data show that distinct members of the BMP family differentially regulate the progression in the osteogenic lineage, and this may be due to their selective affinity for specific receptor complexes...
Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activityP ten Dijke
Ludwig Institute for Cancer Research, Uppsala, Sweden
Oncogene 8:2879-87. 1993..These results suggest that each ALK may have different in vivo functions...
Transforming growth factor-beta-mediated mast cell migration depends on mitogen-activated protein kinase activityN Olsson
Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, S-751 85, Uppsala, Sweden
Cell Signal 13:483-90. 2001..These results indicate that different signalling pathways mediate TGF-beta1-induced migration and growth inhibition in HMC-1 cells, where the migration involves MEK activity...
Apoptosis in podocytes induced by TGF-beta and Smad7M Schiffer
Division of Nephrology, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA
J Clin Invest 108:807-16. 2001..Our results suggest a novel functional role for Smad7 as amplifier of TGF-beta-induced apoptosis in podocytes and a new pathomechanism for podocyte depletion in progressive glomerulosclerosis...
Diffusion of nodal signaling activity in the absence of the feedback inhibitor Lefty2C Meno
Division of Molecular Biology, Institute for Molecular and Cellular Biology, Osaka University, Japan
Dev Cell 1:127-38. 2001..These results suggest that Nodal is a long-range signaling molecule but that its range of action is normally limited by the feedback inhibitor Lefty2...
Bone morphogenetic protein signalling in NGF-stimulated PC12 cellsS Althini
Department of Neuroscience, Uppsala University, Biomedical Centre, Box 587, SE-751 23, Uppsala, Sweden
Biochem Biophys Res Commun 307:632-9. 2003..Hence, NGF and BMP signals are likely to interact further downstream at the transcriptional level in neuronal differentiation of the PC12 cells...
ELAC2, a putative prostate cancer susceptibility gene product, potentiates TGF-beta/Smad-induced growth arrest of prostate cellsD Noda
Department of Experimental Pathology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan
Oncogene 25:5591-600. 2006..Furthermore, activation of the p21 CDK inhibitor promoter by TGF-beta is potentiated by ELAC2. Taken together our data indicate an important transcriptional scaffold function for ELAC2 in TGF-beta/Smad signaling mediated growth arrest...
Reversible ubiquitination regulates the Smad/TGF-beta signalling pathwayS J Wicks
School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK
Biochem Soc Trans 34:761-3. 2006..Studies are currently under way using activity-based HA (haemagglutinin)-tagged ubiquitin probes to identify the full spectrum of DUBs that impact on Smad/TGF-beta signalling activity...
Promoting bone morphogenetic protein signaling through negative regulation of inhibitory SmadsF Itoh
Division of Cellular Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
EMBO J 20:4132-42. 2001..The data strongly suggest that the molecular mechanism by which AMSH exerts its action is by inhibiting the binding of Smad6 to activated type I receptors or activated R-Smads...
Abnormal angiogenesis but intact hematopoietic potential in TGF-beta type I receptor-deficient miceJ Larsson
Molecular Medicine and Gene Therapy, Institute of Laboratory Medicine and Department of Medicine, Lund University Hospital, Lund, Sweden
EMBO J 20:1663-73. 2001....
Assignment1 of the Smad7 gene (MADH7) to human chromosome 18q21.1 by fluorescence in situ hybridizationE Roijer
Laboratory of Cancer Genetics, Department of Pathology, Goteborg University, Sahlgrenska University Hospital, Goteborg, Sweden
Cytogenet Cell Genet 81:189-90. 1998
Induction of inhibitory Smad6 and Smad7 mRNA by TGF-beta family membersM Afrakhte
Unit of Pathology, University Hospital, Uppsala, S 751 85, Sweden
Biochem Biophys Res Commun 249:505-11. 1998..Thus, expression of inhibitory Smads is induced by multiple stimuli, including the various TGF-beta family members, whose action they antagonize...
TGF-beta signalling from cell membrane to nucleus through SMAD proteinsC H Heldin
Ludwig Institute for Cancer Research, Biomedical Centre, Uppsala, Sweden
Nature 390:465-71. 1997..Inhibitory SMADs have been identified that block the activation of these pathway-restricted SMADs...
Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signallingA Nakao
Ludwig Institute for Cancer Research, Uppsala, Sweden
Nature 389:631-5. 1997..TGF-beta rapidly induces expression of Smad7 mRNA, suggesting that Smad7 may participate in a negative feedback loop to control TGF-beta responses...
Identification of Smad2, a human Mad-related protein in the transforming growth factor beta signaling pathwayA Nakao
Ludwig Institute for Cancer Research, Box 595, S 751 24 Uppsala, Sweden
J Biol Chem 272:2896-900. 1997..Smad2 is closely linked to DPC4 on chromosome 18q21.1, a region often deleted in human cancers. Cells that lack Smad2 may escape from TGF-beta-mediated growth inhibition and promote cancer progression...
Phosphorylation of Ser165 in TGF-beta type I receptor modulates TGF-beta1-induced cellular responsesS Souchelnytskyi
Ludwig Institute for Cancer Research, Uppsala, Sweden
EMBO J 15:6231-40. 1996..Mutations of Ser165 changed the phosphorylation pattern of TbetaR-I. These observations suggest that TGF-beta receptor signaling specificity is modulated by phosphorylation of Ser165 of TbetaR-I...
Cloning of a TGF beta type I receptor that forms a heteromeric complex with the TGF beta type II receptorP Franzen
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden
Cell 75:681-92. 1993..These results suggest that signal transduction by TGF beta involves the formation of a heteromeric complex of two different serine/threonine kinase receptors...
Characterization of type I receptors for transforming growth factor-beta and activinP ten Dijke
Ludwig Institute for Cancer Research, Uppsala, Sweden
Science 264:101-4. 1994....
Identification of type I receptors for osteogenic protein-1 and bone morphogenetic protein-4P ten Dijke
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden
J Biol Chem 269:16985-8. 1994..These results suggest that ALK-3 and ALK-6 are type I receptors for OP-1 and BMP-4; in addition, ALK-2 is a type I receptor shared by activin and OP-1, but not by BMP-4...
Identification and characterization of LTBP-2, a novel latent transforming growth factor-beta-binding proteinA Moren
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden
J Biol Chem 269:32469-78. 1994..The LTBP-2 gene was assigned to chromosome 14q24. These results indicate that different forms of latent TGF-beta complexes occur and suggest that the different associated proteins may function to target the complexes to specific sites...
Distinct spatial and temporal expression patterns of two type I receptors for bone morphogenetic proteins during mouse embryogenesisN Dewulf
Laboratory of Molecular Biology Celgen, University of Leuven, Belgium
Endocrinology 136:2652-63. 1995..In addition, the expression of these genes in many soft tissues suggests broader functions for BMPs in embryogenesis...
Physical and functional interaction of murine and Xenopus Smad7 with bone morphogenetic protein receptors and transforming growth factor-beta receptorsS Souchelnytskyi
Ludwig Institute for Cancer Research, Biomedical Center, S 751 24 Uppsala, Sweden
J Biol Chem 273:25364-70. 1998..Our results are consistent with the possibility that the C-domain of antagonistic Smads is an effector domain whereas the N-domain may confer specificity for distinct signaling pathways...
Transforming growth factor beta1 induces nuclear export of inhibitory Smad7S Itoh
Ludwig Institute for Cancer Research, Biomedical Center Box 595, S 751 24 Uppsala, Sweden
J Biol Chem 273:29195-201. 1998..This suggests that an intact Mad homology 2 domain is important for nuclear localization of Smad7. The nuclear localization of Smad7 suggests a functional role distinct from its antagonistic effect in receptor-mediated Smad activation...
Chromosomal localization of three human genes encoding bone morphogenetic protein receptorsA K Aström
Laboratory of Cancer Genetics, Department of Pathology, Goteborg University, Sahlgrenska University Hospital, SE 413 45 Goteborg, Sweden
Mamm Genome 10:299-302. 1999..Using somatic cell hybrid and FISH analyses, the BMPR1A, BMPR1B, and BMPR2 genes were assigned to 10q23, 4q22-24, and 2q33-34, respectively. A processed BMPR1A pseudogene was mapped to 6q23...
SMAD3 represses androgen receptor-mediated transcriptionS A Hayes
Department of Surgery, Stanford University School of Medicine, California 94303, USA
Cancer Res 61:2112-8. 2001..These results provide fresh insight for understanding the mechanism by which TGF-beta regulates the androgen-signaling pathway in prostate cancer cells...
Regulation of Smad signaling by protein kinase CI Yakymovych
Ludwig Institute for Cancer Research, Box 595, Uppsala, Sweden
FASEB J 15:553-5. 2001..Thus, PKC-dependent phosphorylation of Smad3 leads to down-regulation of the growth inhibitory and apoptotic action of TGF-b...
Phosphorylation of Smad signaling proteins by receptor serine/threonine kinasesS Souchelnytskyi
Biomedical Center, Ludwig Institute for Cancer Research, Uppsala, Sweden
Methods Mol Biol 124:107-20. 2001
The orphan receptor serine/threonine kinase ALK7 signals arrest of proliferation and morphological differentiation in a neuronal cell lineH Jornvall
Division of Molecular Neurobiology, Department of Neuroscience, Karolinska Institute, S 17177 Stockholm, Sweden
J Biol Chem 276:5140-6. 2001..These results indicate that ALK7 may participate in the control of proliferation of neuronal precursors and morphological differentiation of postmitotic neurons...
The transcriptional co-activator P/CAF potentiates TGF-beta/Smad signalingS Itoh
The Netherlands Cancer Institute, Division of Cellular Biochemistry, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Nucleic Acids Res 28:4291-8. 2000..Our results indicate a direct physical and functional interplay between two negative regulators of cell proliferation, Smad3 and P/CAF...
Nodal signaling uses activin and transforming growth factor-beta receptor-regulated SmadsA Kumar
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
J Biol Chem 276:656-61. 2001..We also show here that the extracellular cripto protein is required for nodal signaling, making it distinct from activin or TGF-beta signaling...
Expression of the inhibitory Smad7 in early mouse development and upregulation during embryonic vasculogenesisA Zwijsen
Department of Cell Growth, Differentiation, and Development VIB07, Flanders Interuniversity Institute for Biotechnology, University of Leuven, Leuven, Belgium
Dev Dyn 218:663-70. 2000..This confirms earlier conclusions of similar, but complementary, experiments using a dominant negative type II TGF beta receptor demonstrating that TGF beta signalling is required for normal preimplantation development...
Role of Smad proteins and transcription factor Sp1 in p21(Waf1/Cip1) regulation by transforming growth factor-betaK Pardali
Ludwig Institute for Cancer Research, Box 595, SE 751 24 Uppsala, Sweden
J Biol Chem 275:29244-56. 2000..In conclusion, Smad proteins play important roles in regulation of the p21 gene by TGF-beta, and the functional cooperation of Smad proteins with Sp1 involves the physical interaction of these two types of transcription factors...
Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesisS P Oh
Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA 02129, USA
Proc Natl Acad Sci U S A 97:2626-31. 2000..Taken together, our results suggest that the balance between the ALK1 and ALK5 signaling pathways in endothelial cells plays a crucial role in determining vascular endothelial properties during angiogenesis...
Hedgehog creates a gradient of DPP activity in Drosophila wing imaginal discsH Tanimoto
Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan
Mol Cell 5:59-71. 2000..We suggest that regulation of tkv by HH is a key part of the mechanism that controls the level and distribution of DPP...
Smad and AML proteins synergistically confer transforming growth factor beta1 responsiveness to human germ-line IgA genesE Pardali
Division of Tumor Biology, Department of Cell and Molecular Biology, Umea University, S 901 87 Umea, Sweden
J Biol Chem 275:3552-60. 2000..Considering the wide range of biological phenomena that AMLs and Smads regulate, the physical/functional interplay between them has implications that extend beyond the regulation of class switching to IgA...
Cloning and characterization of a human type II receptor for bone morphogenetic proteinsB L Rosenzweig
Synergen, Inc, Boulder, CO 80301 2546, USA
Proc Natl Acad Sci U S A 92:7632-6. 1995..Binding of OP-1/BMP-7 to BMPR-II was also observed in nontransfected cell lines. Moreover, a transcriptional activation signal was transduced by BMPR-II in the presence of type I receptors after stimulation by OP-1/BMP-7...
