Carl Henrik Heldin

Summary

Affiliation: Ludwig Institute for Cancer Research
Country: Sweden

Publications

  1. ncbi request reprint High interstitial fluid pressure - an obstacle in cancer therapy
    Carl Henrik Heldin
    Ludwig Institute for Cancer Research, Box 595, SE 751 24 Uppsala, Sweden
    Nat Rev Cancer 4:806-13. 2004
  2. pmc Interaction between Smad7 and beta-catenin: importance for transforming growth factor beta-induced apoptosis
    Sofia Edlund
    Ludwig Institute for Cancer Research, Box 595, Biomedical Center, SE 751 24 Uppsala, Sweden
    Mol Cell Biol 25:1475-88. 2005
  3. pmc Autocrine PDGF stimulation in malignancies
    Carl Henrik Heldin
    Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden
    Ups J Med Sci 117:83-91. 2012
  4. doi request reprint Targeting the PDGF signaling pathway in the treatment of non-malignant diseases
    Carl Henrik Heldin
    Ludwig Institute for Cancer Research Ltd, Science for Life Laboratory, Uppsala University, Box 595, SE 75124, Uppsala, Sweden
    J Neuroimmune Pharmacol 9:69-79. 2014
  5. pmc Targeting the PDGF signaling pathway in tumor treatment
    Carl Henrik Heldin
    Ludwig Institute for Cancer Research, Science for Life Laboratory, Uppsala University, Box 595SE 751 24 Uppsala, Sweden
    Cell Commun Signal 11:97. 2013
  6. pmc Structural and functional properties of platelet-derived growth factor and stem cell factor receptors
    Carl Henrik Heldin
    Ludwig Institute for Cancer Research, Uppsala University, SE 751 24 Uppsala, Sweden
    Cold Spring Harb Perspect Biol 5:a009100. 2013
  7. pmc Platelet-derived growth factor-induced Akt phosphorylation requires mTOR/Rictor and phospholipase C-γ1, whereas S6 phosphorylation depends on mTOR/Raptor and phospholipase D
    Masoud Razmara
    Ludwig Institute for Cancer Research, Science for Life Laboratory, Box 595, Biomedical Center, SE 751 24, Uppsala, Sweden
    Cell Commun Signal 11:3. 2013
  8. doi request reprint Regulation of EMT by TGFβ in cancer
    Carl Henrik Heldin
    Ludwig Institute for Cancer Research, Uppsala University, Box 595, SE 751 24 Uppsala, Sweden
    FEBS Lett 586:1959-70. 2012
  9. pmc Emergence, development and diversification of the TGF-beta signalling pathway within the animal kingdom
    Lukasz Huminiecki
    Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden
    BMC Evol Biol 9:28. 2009
  10. pmc Smad7 and protein phosphatase 1alpha are critical determinants in the duration of TGF-beta/ALK1 signaling in endothelial cells
    Gudrun Valdimarsdottir
    Dept of Biochemistry and Molecular Biology, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik, Iceland
    BMC Cell Biol 7:16. 2006

Collaborators

Detail Information

Publications108 found, 100 shown here

  1. ncbi request reprint High interstitial fluid pressure - an obstacle in cancer therapy
    Carl Henrik Heldin
    Ludwig Institute for Cancer Research, Box 595, SE 751 24 Uppsala, Sweden
    Nat Rev Cancer 4:806-13. 2004
    ..Lowering the tumour IFP with specific signal-transduction antagonists might be a useful approach to improving anticancer drug efficacy...
  2. pmc Interaction between Smad7 and beta-catenin: importance for transforming growth factor beta-induced apoptosis
    Sofia Edlund
    Ludwig Institute for Cancer Research, Box 595, Biomedical Center, SE 751 24 Uppsala, Sweden
    Mol Cell Biol 25:1475-88. 2005
    ....
  3. pmc Autocrine PDGF stimulation in malignancies
    Carl Henrik Heldin
    Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden
    Ups J Med Sci 117:83-91. 2012
    ..Patients with such tumors could benefit from treatment with inhibitors of either PDGF or PDGF receptors...
  4. doi request reprint Targeting the PDGF signaling pathway in the treatment of non-malignant diseases
    Carl Henrik Heldin
    Ludwig Institute for Cancer Research Ltd, Science for Life Laboratory, Uppsala University, Box 595, SE 75124, Uppsala, Sweden
    J Neuroimmune Pharmacol 9:69-79. 2014
    ..The present communication summarizes the use of PDGF antagonists in the treatment of non-malignant diseases. ..
  5. pmc Targeting the PDGF signaling pathway in tumor treatment
    Carl Henrik Heldin
    Ludwig Institute for Cancer Research, Science for Life Laboratory, Uppsala University, Box 595SE 751 24 Uppsala, Sweden
    Cell Commun Signal 11:97. 2013
    ..Whether treatment with PDGF/PDGF receptor antagonists will be beneficial for more common malignancies is the subject for ongoing studies. ..
  6. pmc Structural and functional properties of platelet-derived growth factor and stem cell factor receptors
    Carl Henrik Heldin
    Ludwig Institute for Cancer Research, Uppsala University, SE 751 24 Uppsala, Sweden
    Cold Spring Harb Perspect Biol 5:a009100. 2013
    ....
  7. pmc Platelet-derived growth factor-induced Akt phosphorylation requires mTOR/Rictor and phospholipase C-γ1, whereas S6 phosphorylation depends on mTOR/Raptor and phospholipase D
    Masoud Razmara
    Ludwig Institute for Cancer Research, Science for Life Laboratory, Box 595, Biomedical Center, SE 751 24, Uppsala, Sweden
    Cell Commun Signal 11:3. 2013
    ..mTORC1 is activated in a PLD-dependent manner and promotes phosphorylation of the S6 protein, whereas mTORC2, in concert with PLCγ signaling, promotes Akt phosphorylation...
  8. doi request reprint Regulation of EMT by TGFβ in cancer
    Carl Henrik Heldin
    Ludwig Institute for Cancer Research, Uppsala University, Box 595, SE 751 24 Uppsala, Sweden
    FEBS Lett 586:1959-70. 2012
    ..The EMT program has certain similarities with the stem cell program. Inducers and effectors of EMT are interesting targets for the development of improved diagnosis, prognosis and therapy of cancer...
  9. pmc Emergence, development and diversification of the TGF-beta signalling pathway within the animal kingdom
    Lukasz Huminiecki
    Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden
    BMC Evol Biol 9:28. 2009
    ..Herein, we focus on the diversification of the transforming growth factor-beta (TGF-beta) pathway -- one of the fundamental and versatile metazoan signal transduction engines...
  10. pmc Smad7 and protein phosphatase 1alpha are critical determinants in the duration of TGF-beta/ALK1 signaling in endothelial cells
    Gudrun 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...
  11. pmc Clinicopathological significance of platelet-derived growth factor (PDGF)-B and vascular endothelial growth factor-A expression, PDGF receptor-β phosphorylation, and microvessel density in gastric cancer
    Shioto Suzuki
    Department of Molecular and Cellular Pathology, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan
    BMC Cancer 10:659. 2010
    ....
  12. doi request reprint The European Research Council--a new opportunity for European science
    Carl Henrik Heldin
    Ludwig Institute for Cancer Research, Uppsala University, Box 595, SE 751 24 Uppsala, Sweden
    Nat Rev Mol Cell Biol 9:417-20. 2008
    ..With a focus on excellence, calls for both young and experienced scientists and an average budget of \[euro]1 billion per year, the ERC will have the opportunity to give basic research in Europe a significant boost...
  13. ncbi request reprint Mechanism of action and in vivo role of platelet-derived growth factor
    C H Heldin
    Ludwig Institute for Cancer Research, Biomedical Center, and Department of Pathology, University Hospital, Uppsala, Sweden
    Physiol Rev 79:1283-316. 1999
    ..This review discusses structural and functional properties of PDGF and PDGF receptors, the mechanism whereby PDGF exerts its cellular effects, and the role of PDGF in normal and diseased tissues...
  14. doi request reprint Mechanism of TGF-beta signaling to growth arrest, apoptosis, and epithelial-mesenchymal transition
    Carl Henrik Heldin
    Ludwig Institute for Cancer Research, Uppsala University, BMC, Uppsala, Sweden
    Curr Opin Cell Biol 21:166-76. 2009
    ..The aim of this review is to summarize some of the recent findings on the mechanism of TGF-beta signaling to growth arrest, apoptosis, and epithelial-mesenchymal transition...
  15. doi request reprint Role of Smads in TGFβ signaling
    Carl Henrik Heldin
    Ludwig Institute for Cancer Research, Uppsala University, Box 595, SE 751 24 Uppsala, Sweden
    Cell Tissue Res 347:21-36. 2012
    ..The Smad function has been shown to be perturbed in certain diseases such as cancer...
  16. ncbi request reprint Signal transduction: multiple pathways, multiple options for therapy
    C H Heldin
    Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden
    Stem Cells 19:295-303. 2001
    ..Thus, antagonists of several signaling pathways have potential clinical utility. Several such compounds are currently used or are in clinical trials; others are currently being analyzed in animal models...
  17. pmc Nuclear factor YY1 inhibits transforming growth factor beta- and bone morphogenetic protein-induced cell differentiation
    Keiko Kurisaki
    Ludwig Institute for Cancer Research, Biomedical Center, SE 751 24 Uppsala, Sweden
    Mol Cell Biol 23:4494-510. 2003
    ..In conclusion, YY1 represses Smad transcriptional activities in a gene-specific manner and thus regulates cell differentiation induced by TGF-beta superfamily pathways...
  18. pmc Transforming growth factor-beta1 (TGF-beta)-induced apoptosis of prostate cancer cells involves Smad7-dependent activation of p38 by TGF-beta-activated kinase 1 and mitogen-activated protein kinase kinase 3
    Sofia Edlund
    Ludwig Institute for Cancer Research, Biomedical Centre, 75124 Uppsala, Sweden
    Mol Biol Cell 14:529-44. 2003
    ..Moreover, ectopically expressed Smad7 enhanced the coimmunoprecipitation of HA-MKK3 and Flag-p38, supporting the notion that Smad7 may act as a scaffolding protein and facilitate TAK1- and MKK3-mediated activation of p38...
  19. ncbi request reprint Gab1 contributes to cytoskeletal reorganization and chemotaxis in response to platelet-derived growth factor
    Anders Kallin
    Ludwig Institute for Cancer Research, Biomedical Center, SE 751 24 Uppsala, Sweden
    J Biol Chem 279:17897-904. 2004
    ..In conclusion, Gab1 plays a selective role in the regulation of the mitogen-activated protein kinases Erk and p38 downstream of the PDGF beta-receptor, and contributes to cytoskeletal reorganization and chemotaxis in response to PDGF...
  20. ncbi request reprint Differential ubiquitination defines the functional status of the tumor suppressor Smad4
    Anita Morén
    Ludwig Institute for Cancer Research, Box 595, Biomedical Center, SE 751 24 Uppsala, Sweden
    J Biol Chem 278:33571-82. 2003
    ..These data suggest that oligo-ubiquitination positively regulates Smad4 function, whereas poly-ubiquitination primarily occurs in unstable cancer mutants and leads to protein degradation...
  21. ncbi request reprint A gain of function mutation in the activation loop of platelet-derived growth factor beta-receptor deregulates its kinase activity
    Federica Chiara
    Ludwig Institute for Cancer Research, Box 595, Uppsala S 751 24, Sweden
    J Biol Chem 279:42516-27. 2004
    ..Our findings support a model whereby an activating point mutation results in a deregulated PDGFRbeta with oncogenic predisposition...
  22. pmc Transforming growth factor-beta-induced mobilization of actin cytoskeleton requires signaling by small GTPases Cdc42 and RhoA
    Sofia Edlund
    Ludwig Institute for Cancer Research, Biomedical Center, S 751 24 Uppsala, Sweden
    Mol Biol Cell 13:902-14. 2002
    ..Collectively, these data indicate that TGF-beta-induced membrane ruffles occur via Rho GTPase-dependent pathways, whereas long-term effects require cooperation between Smad and Rho GTPase signaling pathways...
  23. ncbi request reprint Inhibition of transforming growth factor-beta signaling by low molecular weight compounds interfering with ATP- or substrate-binding sites of the TGF beta type I receptor kinase
    Ihor Yakymovych
    Ludwig Institute for Cancer Research, Box 595, SE 751 24 Uppsala, Sweden
    Biochemistry 41:11000-7. 2002
    ..Thus, the substrate-mimetic peptide is a new type of specific inhibitor of the TGFbeta signaling in vivo...
  24. ncbi request reprint The balance between acetylation and deacetylation controls Smad7 stability
    Maria Simonsson
    Ludwig Institute for Cancer Research, Box 595, Husargatan 3, S 751 24 Uppsala, Sweden
    J Biol Chem 280:21797-803. 2005
    ....
  25. pmc Functional proteomics of transforming growth factor-beta1-stimulated Mv1Lu epithelial cells: Rad51 as a target of TGFbeta1-dependent regulation of DNA repair
    Takashi Kanamoto
    Ludwig Institute for Cancer Research, Box 595, SE 751 24, Uppsala, Sweden
    EMBO J 21:1219-30. 2002
    ..The TGFbeta1-dependent inhibition of DNA repair was reversed by ectopic overexpression of Rad51. Therefore, TGFbeta can promote DNA instability through down-regulation of Rad51 and inhibition of DNA repair...
  26. ncbi request reprint Smad7 is required for TGF-beta-induced activation of the small GTPase Cdc42
    Sofia Edlund
    Ludwig Institute for Cancer Research, Biomedical Center, Box 595, 751 24 Uppsala, Sweden
    J Cell Sci 117:1835-47. 2004
    ..These observations propose a novel role for Smad7 in TGF-beta-dependent activation of Rho GTPases...
  27. ncbi request reprint Control of Smad7 stability by competition between acetylation and ubiquitination
    Eva Grönroos
    Ludwig Institute for Cancer Research, Box 595, Husargatan 3, S 751 24 Uppsala, Sweden
    Mol Cell 10:483-93. 2002
    ..Thus, our data suggest that competition between ubiquitination and acetylation of overlapping lysine residues constitutes a novel mechanism to regulate protein stability...
  28. pmc Id2 and Id3 define the potency of cell proliferation and differentiation responses to transforming growth factor beta and bone morphogenetic protein
    Marcin Kowanetz
    Ludwig Institute for Cancer Research, SE 751 24 Uppsala, Sweden
    Mol Cell Biol 24:4241-54. 2004
    ..Thus, Id genes sense Smad signals and create a permissive or refractory nuclear environment that defines decisions of cell fate and proliferation...
  29. ncbi request reprint BRCA2 and Smad3 synergize in regulation of gene transcription
    Olena Preobrazhenska
    Ludwig Institute for Cancer Research, Box 595, Husargatan, 3, SE 751 24, Uppsala, Sweden
    Oncogene 21:5660-4. 2002
    ..Thus, our results show that BRCA2 and Smad3 form a complex and synergize in regulation of transcription...
  30. pmc Loss of T-cell protein tyrosine phosphatase induces recycling of the platelet-derived growth factor (PDGF) beta-receptor but not the PDGF alpha-receptor
    Susann Karlsson
    Ludwig Institute for Cancer Research, Uppsala University Biomedical Center, S 751 24 Uppsala, Sweden
    Mol Biol Cell 17:4846-55. 2006
    ..Thus, loss of TC-PTP specifically redirects the PDGF beta-receptor toward rapid recycling, which is the first evidence of differential trafficking of PDGF receptor family members...
  31. pmc TGF-beta and the Smad signaling pathway support transcriptomic reprogramming during epithelial-mesenchymal cell transition
    Ulrich Valcourt
    Ludwig Institute for Cancer Research, Uppsala, Sweden
    Mol Biol Cell 16:1987-2002. 2005
    ....
  32. ncbi request reprint SHP-2 is involved in heterodimer specific loss of phosphorylation of Tyr771 in the PDGF beta-receptor
    Simon Ekman
    Ludwig Institute for Cancer Research, Biomedical Center, Box 595, S 751 24, Uppsala, Sweden
    Oncogene 21:1870-5. 2002
    ..Thus, SHP-2 appears to play an important role in modulating phosphorylation of Y771, thereby controlling RasGAP recruitment and Ras/MAP kinase signaling in the heterodimeric configuration of the PDGF receptors...
  33. ncbi request reprint From mono- to oligo-Smads: the heart of the matter in TGF-beta signal transduction
    Aristidis Moustakas
    Ludwig Institute for Cancer Research, SE 751 24 Uppsala, Sweden
    Genes Dev 16:1867-71. 2002
  34. ncbi request reprint Inhibition of PDGF receptor signaling in tumor stroma enhances antitumor effect of chemotherapy
    Kristian Pietras
    Ludwig Institute for Cancer Research, SE 751 24 Uppsala, Sweden
    Cancer Res 62:5476-84. 2002
    ..In conclusion, our study identifies inhibition of PDGF signaling in tumor stroma as a novel, possibly general strategy for enhancement of the therapeutic effects chemotherapy...
  35. ncbi request reprint Degradation of the tumor suppressor Smad4 by WW and HECT domain ubiquitin ligases
    Anita Morén
    Ludwig Institute for Cancer Research, Box 595, Biomedical Center, Uppsala University, SE 751 24 Uppsala, Sweden
    J Biol Chem 280:22115-23. 2005
    ..Such mechanisms of down-regulation of TGF-beta signaling may be critical for proper physiological response to this pathway...
  36. ncbi request reprint Smad2 phosphorylation by type I receptor: contribution of arginine 462 and cysteine 463 In the C terminus of Smad2 for specificity
    Ihor Yakymovych
    Ludwig Institute for Cancer Research, Box 595, SE 751 24 Uppsala, Sweden
    J Biol Chem 279:35781-7. 2004
    ..Thus, Arg-462 and Cys-463, which are in proximity of the C-terminal serine residues, contribute to recognition and phosphorylation of the C terminus of Smad2 by type I TGFbeta receptor...
  37. pmc Ligand-induced recruitment of Na+/H+-exchanger regulatory factor to the PDGF (platelet-derived growth factor) receptor regulates actin cytoskeleton reorganization by PDGF
    Jean Baptiste Demoulin
    Ludwig Institute for Cancer Research, Box 595, SE 75124 Uppsala, Sweden
    Biochem J 376:505-10. 2003
    ..Collectively, these results suggest that the ligand-induced association of NHERF PDZ domain with the PDGF receptor tyrosine kinase controls the extent of cytoskeleton reorganization in response to PDGF...
  38. pmc Phosphoproteome profiling of transforming growth factor (TGF)-beta signaling: abrogation of TGFbeta1-dependent phosphorylation of transcription factor-II-I (TFII-I) enhances cooperation of TFII-I and Smad3 in transcription
    Taras Stasyk
    Ludwig Institute for Cancer Research, Uppsala University, SE 751 24 Uppsala, Sweden
    Mol Biol Cell 16:4765-80. 2005
    ..Thus, TGFbeta1-dependent phosphorylation of TFII-I may modulate TGFbeta signaling at the transcriptional level...
  39. pmc Transcriptional induction of salt-inducible kinase 1 by transforming growth factor β leads to negative regulation of type I receptor signaling in cooperation with the Smurf2 ubiquitin ligase
    Peter Lönn
    Ludwig Institute for Cancer Research, Uppsala University, SE 751 24 Uppsala, Sweden
    J Biol Chem 287:12867-78. 2012
    ..In conclusion, TGFβ induces expression of Smad7, Smurf2, and SIK1, the products of which physically and functionally interlink to control the activity of this pathway...
  40. pmc Intercellular variation in signaling through the TGF-β pathway and its relation to cell density and cell cycle phase
    Agata Zieba
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, SE 75185 Sweden
    Mol Cell Proteomics 11:M111.013482. 2012
    ....
  41. ncbi request reprint STI571 enhances the therapeutic index of epothilone B by a tumor-selective increase of drug uptake
    Kristian Pietras
    Ludwig Institute for Cancer Research, SE 751 24 Uppsala, Sweden
    Clin Cancer Res 9:3779-87. 2003
    ....
  42. pmc The activity of hyaluronan synthase 2 is regulated by dimerization and ubiquitination
    Eugenia Karousou
    Ludwig Institute for Cancer Research, Uppsala University Biomedical Center, SE 75124 Uppsala, Sweden
    J Biol Chem 285:23647-54. 2010
    ..Interestingly, K190R-mutated HAS2 formed dimers with wt HAS2 and quenched the activity of wt HAS2, thus demonstrating a functional role of the dimeric configuration...
  43. ncbi request reprint Autoinhibition of the platelet-derived growth factor beta-receptor tyrosine kinase by its C-terminal tail
    Federica Chiara
    Ludwig Institute for Cancer Research, S 75124 Uppsala, Sweden
    J Biol Chem 279:19732-8. 2004
    ..These findings indicate that allosteric inhibition of the PDGF beta-receptor by its C-terminal tail is one of the mechanisms involved in keeping the receptor inactive in the absence of ligand...
  44. pmc Transforming growth factor-beta employs HMGA2 to elicit epithelial-mesenchymal transition
    Sylvie Thuault
    Ludwig Institute for Cancer Research, Uppsala University, SE 751 24 Uppsala, Sweden, and Institut National de la Sante et de la Recherche Medicale, Hopital E Herriot, Lyon Cedex, France
    J Cell Biol 174:175-83. 2006
    ..This network of signaling/transcription factors that work sequentially to establish EMT suggests that combinatorial detection of these proteins could serve as a new tool for EMT analysis in cancer patients...
  45. pmc Combined anti-angiogenic therapy targeting PDGF and VEGF receptors lowers the interstitial fluid pressure in a murine experimental carcinoma
    Agnieszka Kłosowska-Wardega
    Biomedical Center, Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden
    PLoS ONE 4:e8149. 2009
    ..Simultaneous targeting of VEGFR and PDGFR kinase activity may be a useful strategy to decrease tumor IFP, but the timing of the inhibitors should be carefully determined...
  46. pmc The Fer tyrosine kinase is important for platelet-derived growth factor-BB-induced signal transducer and activator of transcription 3 (STAT3) protein phosphorylation, colony formation in soft agar, and tumor growth in vivo
    Johan Lennartsson
    Ludwig Institute for Cancer Research, Science for Life Laboratory, Uppsala University, Box 595, SE 75124, Uppsala, Sweden
    J Biol Chem 288:15736-44. 2013
    ..Tumor growth in vivo was delayed in cells depleted of Fer expression. Our data suggest a critical role of Fer in PDGF-BB-induced STAT3 activation and cell transformation...
  47. pmc APC and Smad7 link TGFβ type I receptors to the microtubule system to promote cell migration
    Maria Ekman
    Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden
    Mol Biol Cell 23:2109-21. 2012
    ..Moreover, the Smad7-APC complex links the TGFβ type I receptor to the microtubule system to regulate directed cellular extension and migratory responses evoked by TGFβ...
  48. doi request reprint PARP-1 attenuates Smad-mediated transcription
    Peter Lönn
    Ludwig Institute for Cancer Research, Uppsala University, Box 595 Biomedical Center, SE 751 24 Uppsala, Sweden
    Mol Cell 40:521-32. 2010
    ..Thus, our results identify ADP-ribosylation of Smad proteins by PARP-1 as a key step in controlling the strength and duration of Smad-mediated transcription...
  49. pmc Site-selective regulation of platelet-derived growth factor beta receptor tyrosine phosphorylation by T-cell protein tyrosine phosphatase
    Camilla Persson
    Ludwig Institute for Cancer Research, Uppsala Branch, Biomedical Center, S 751 24 Uppsala, Sweden
    Mol Cell Biol 24:2190-201. 2004
    ..In summary, our findings identify TC-PTP as a previously unrecognized negative regulator of PDGF beta receptor signaling and support the general notion that PTPs display site selectivity in their action on tyrosine kinase receptors...
  50. ncbi request reprint Smad pathway-specific transcriptional regulation of the cell cycle inhibitor p21(WAF1/Cip1)
    Katerina Pardali
    Ludwig Institute for Cancer Research, Uppsala, Sweden
    J Cell Physiol 204:260-72. 2005
    ..Thus, p21 is a common target of all TGF-beta superfamily pathways. However, the ability of TGF-beta superfamily members to induce cell growth arrest depends on the regulation of additional gene targets...
  51. ncbi request reprint c-Jun N-terminal kinase is necessary for platelet-derived growth factor-mediated chemotaxis in primary fibroblasts
    Kenichi Amagasaki
    Ludwig Institute for Cancer Research, Uppsala University, Box 595, Biomedical Center, SE 751 24 Uppsala, Sweden
    J Biol Chem 281:22173-9. 2006
    ..In conclusion, JNK is a critical component downstream of PI 3-kinase that may be involved in PDGF-stimulated chemotaxis presumably by modulating the integrity of focal adhesions by phosphorylating its components...
  52. ncbi request reprint TGFbeta1-induced activation of ATM and p53 mediates apoptosis in a Smad7-dependent manner
    Shouting Zhang
    Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Uppsala, Sweden
    Cell Cycle 5:2787-95. 2006
    ..Our data imply that Smad7 plays a crucial role upstream of ATM and p53 to protect the genome from insults evoked by extracellular stress...
  53. doi request reprint Mutation of tyrosine residue 857 in the PDGF beta-receptor affects cell proliferation but not migration
    Piotr Wardega
    Ludwig Institute for Cancer Research, Uppsala University, Biomedical Center, Uppsala, Sweden
    Cell Signal 22:1363-8. 2010
    ..Interestingly, PDGFRbeta(Y857F) was unable to mediate PDGF-BB-induced mitogenic signaling, whereas it could elicit a chemotactic response...
  54. pmc Notch signaling is necessary for epithelial growth arrest by TGF-beta
    Hideki Niimi
    Ludwig Institute for Cancer Research, Biomedical Center, Uppsala University, SE 751 24 Uppsala, Sweden
    J Cell Biol 176:695-707. 2007
    ..We establish an intimate involvement of Notch signaling in the epithelial cytostatic response to TGF-beta...
  55. ncbi request reprint Platelet-derived growth factor production by B16 melanoma cells leads to increased pericyte abundance in tumors and an associated increase in tumor growth rate
    Masao Furuhashi
    Ludwig Institute for Cancer Research, Uppsala Branch, Uppsala, Sweden
    Cancer Res 64:2725-33. 2004
    ..Our findings thus demonstrate that paracrine PDGF production stimulates pericyte recruitment to tumor vessels and suggest that pericyte abundance influences tumor cell apoptosis and tumor growth...
  56. pmc Preferential oxidation of the second phosphatase domain of receptor-like PTP-alpha revealed by an antibody against oxidized protein tyrosine phosphatases
    Camilla Persson
    Ludwig Institute for Cancer Research, Box 595, SE 751 24 Uppsala, Sweden
    Proc Natl Acad Sci U S A 101:1886-91. 2004
    ....
  57. ncbi request reprint Alix facilitates the interaction between c-Cbl and platelet-derived growth factor beta-receptor and thereby modulates receptor down-regulation
    Johan Lennartsson
    Ludwig Institute for Cancer Research, Uppsala University, Biomedical Center, SE 751 24 Uppsala, Sweden
    J Biol Chem 281:39152-8. 2006
    ..Our data suggest that Alix inhibits down-regulation of PDGFRbeta by modulating the interaction between c-Cbl and the receptor, thereby affecting the ubiquitination of the receptor...
  58. pmc HMGA2 and Smads co-regulate SNAIL1 expression during induction of epithelial-to-mesenchymal transition
    Sylvie Thuault
    Ludwig Institute for Cancer Research, Box 595 Biomedical Center, Uppsala University, SE 751 24 Uppsala, Sweden
    J Biol Chem 283:33437-46. 2008
    ..The data propose that HMGA2 acts in a gene-specific manner to orchestrate the transcriptional network necessary for the EMT program...
  59. pmc Transforming growth factor beta promotes complexes between Smad proteins and the CCCTC-binding factor on the H19 imprinting control region chromatin
    Rosita Bergstrom
    Ludwig Institute for Cancer Research, Uppsala University, SE 751 24 Uppsala, Sweden
    J Biol Chem 285:19727-37. 2010
    ..Because the CTCF-Smad complex is not essential for the chromatin insulator function of the H19 ICR, we propose that it can play a role in chromatin cross-talk organized by the H19 ICR...
  60. ncbi request reprint Inhibition of platelet-derived growth factor-BB-induced receptor activation and fibroblast migration by hyaluronan activation of CD44
    Lingli Li
    Ludwig Institute for Cancer Research, Uppsala University, Biomedical Center, Box 595, S 751 24 Uppsala, Sweden
    J Biol Chem 281:26512-9. 2006
    ..Our observations suggest that hyaluronan suppresses PDGF beta-receptor activation by recruiting a CD44-associated tyrosine phosphatase to the receptor...
  61. ncbi request reprint The DNA binding activities of Smad2 and Smad3 are regulated by coactivator-mediated acetylation
    Maria Simonsson
    Ludwig Institute for Cancer Research, Uppsala University, Biomedical Center, Box 595, Husargatan 3, S 751 24 Uppsala, Sweden
    J Biol Chem 281:39870-80. 2006
    ..Thus, coactivator-mediated acetylation of receptor-activated Smad molecules could represent a novel way to regulate TGFbeta signaling...
  62. ncbi request reprint TGFbeta1/Smad3 counteracts BRCA1-dependent repair of DNA damage
    Anna Dubrovska
    Ludwig Institute for Cancer Research, Box 595, Biomedical Center, SE 751 24 Uppsala, Sweden
    Oncogene 24:2289-97. 2005
    ..Thus, TGFbeta1/Smad3 suppresses BRCA1-dependent DNA repair in response to a DNA damaging agent...
  63. doi request reprint Induction of epithelial-mesenchymal transition by transforming growth factor β
    Aristidis Moustakas
    Ludwig Institute for Cancer Research, Science for Life Laboratory, Uppsala University, SE 751 24 Uppsala, Sweden
    Semin Cancer Biol 22:446-54. 2012
    ....
  64. ncbi request reprint Oral imatinib mesylate (STI571/gleevec) improves the efficacy of local intravascular vascular endothelial growth factor-C gene transfer in reducing neointimal growth in hypercholesterolemic rabbits
    Olli Leppanen
    Ludwig Institute for Cancer Research, Uppsala, Sweden
    Circulation 109:1140-6. 2004
    ....
  65. pmc Regulation of transcription factor Twist expression by the DNA architectural protein high mobility group A2 during epithelial-to-mesenchymal transition
    E Jean Tan
    Ludwig Institute for Cancer Research, Biomedical Center, Uppsala University, Uppsala SE 751 24, Sweden
    J Biol Chem 287:7134-45. 2012
    ....
  66. pmc Polyubiquitination of transforming growth factor β (TGFβ)-associated kinase 1 mediates nuclear factor-κB activation in response to different inflammatory stimuli
    Anahita Hamidi
    Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden
    J Biol Chem 287:123-33. 2012
    ..7 after LPS treatment. In conclusion, polyubiquitination of TAK1 is correlated with activation of TAK1 and is essential for activation of NF-κB signaling downstream of several receptors...
  67. pmc Smad7 regulates the adult neural stem/progenitor cell pool in a transforming growth factor beta- and bone morphogenetic protein-independent manner
    Monika Krampert
    Ludwig Institute for Cancer Research, Uppsala University, Box 595, BMC, 75124 Uppsala, Sweden
    Mol Cell Biol 30:3685-94. 2010
    ..Conversely, an EGF receptor inhibitor reduced the proliferation of these cells. Our data indicate that endogenous Smad7 regulates neural stem/progenitor cell proliferation in a TGF-beta- and BMP-independent manner...
  68. pmc Growth factor regulation of hyaluronan synthesis and degradation in human dermal fibroblasts: importance of hyaluronan for the mitogenic response of PDGF-BB
    Lingli Li
    Ludwig Institute for Cancer Research, Uppsala University, Biomedical Center, Box 595, S 751 24 Uppsala, Sweden
    Biochem J 404:327-36. 2007
    ..We conclude that the ERK MAPK and PI3K signalling pathways are necessary for the regulation of hyaluronan synthesis by PDGF-BB, and that prevention of its binding to CD44 inhibits PDGF-BB-induced cell growth...
  69. ncbi request reprint PDGF receptors as cancer drug targets
    Kristian Pietras
    Ludwig Institute for Cancer Research, Uppsala, Sweden
    Cancer Cell 3:439-43. 2003
  70. ncbi request reprint Bone morphogenetic protein-7 (OP1) and transforming growth factor-beta1 modulate 1,25(OH)2-vitamin D3-induced differentiation of human osteoblasts
    Annegret Eichner
    Ludgwig Institute for Cancer Research, Uppsala, Sweden
    Exp Cell Res 275:132-42. 2002
    ..Our results suggest that 1,25(OH)2-vitamin D3 modulates in opposite ways the effects of BMP7 and TGFbeta1 on osteoblast differentiation...
  71. pmc The mechanism of nuclear export of Smad3 involves exportin 4 and Ran
    Akira Kurisaki
    Ludwig Institute for Cancer Research, Box 595 Biomedical Center, SE 751 24 Uppsala, Sweden
    Mol Cell Biol 26:1318-32. 2006
    ..A short peptide representing the minimal interaction domain in Smad3 effectively competes with Smad3 association to exportin 4 and blocks nuclear export of Smad3 in vivo. We thus delineate a novel nuclear export pathway for Smad3...
  72. pmc TGFbeta induces SIK to negatively regulate type I receptor kinase signaling
    Marcin Kowanetz
    Ludwig Institute for Cancer Research, Uppsala University, Box 595 Biomedical Center, Uppsala, Sweden
    J Cell Biol 182:655-62. 2008
    ..Loss of endogenous SIK results in enhanced gene responses of the fibrotic and cytostatic programs of TGFbeta. We thus identify in SIK a negative regulator that controls TGFbeta receptor turnover and physiological signaling...
  73. doi request reprint MKP3 negatively modulates PDGF-induced Akt and Erk5 phosphorylation as well as chemotaxis
    Masoud Razmara
    Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden
    Cell Signal 24:635-40. 2012
    ....
  74. ncbi request reprint TGF-beta signaling from a three-dimensional perspective: insight into selection of partners
    Serhiy Souchelnytskyi
    Ludwig Institute for Cancer Research, Box 595, Husargatan 3, SE 751 24, Uppsala, Sweden
    Trends Cell Biol 12:304-7. 2002
    ....
  75. ncbi request reprint Identification of a subset of pericytes that respond to combination therapy targeting PDGF and VEGF signaling
    Yoko Hasumi
    Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden
    Int J Cancer 121:2606-14. 2007
    ....
  76. ncbi request reprint Platelet-derived growth factor stimulates membrane lipid synthesis through activation of phosphatidylinositol 3-kinase and sterol regulatory element-binding proteins
    Jean Baptiste Demoulin
    Ludwig Institute for Cancer Research, Uppsala Branch, Biomedical Centre, Box 595, SE 75124 Uppsala, Sweden
    J Biol Chem 279:35392-402. 2004
    ..In conclusion, our results suggest that growth factors induce membrane lipid synthesis via the activation SREBP and PI3K...
  77. ncbi request reprint Non-Smad TGF-beta signals
    Aristidis Moustakas
    Ludwig Institute for Cancer Research, Biomedical Center, Uppsala University, Box 595, SE 751 24 Uppsala, Sweden
    J Cell Sci 118:3573-84. 2005
    ....
  78. ncbi request reprint Deletion of exon I of SMAD7 in mice results in altered B cell responses
    Ronggui Li
    Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden
    J Immunol 176:6777-84. 2006
    ..Interestingly, LPS treatment reverted the apoptotic phenotype in the mutant cells. Taken together, the observed phenotype highlights a prominent role for Smad7 in development and in regulating the immune system's response to TGF-beta...
  79. ncbi request reprint An activating mutation in the PDGF receptor-beta causes abnormal morphology in the mouse placenta
    Camilla Looman
    Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden
    Int J Dev Biol 51:361-70. 2007
    ..In addition, the fetal blood vessel compartment of the labyrinth was completely disorganized...
  80. ncbi request reprint Signaling networks guiding epithelial-mesenchymal transitions during embryogenesis and cancer progression
    Aristidis Moustakas
    Ludwig Institute for Cancer Research, Uppsala University, Box 595 Biomedical Center, SE 751 24 Uppsala, Sweden
    Cancer Sci 98:1512-20. 2007
    ..Here we present some of the current mechanisms that mediate the process of EMT and discuss their relevance to cancer progression...
  81. doi request reprint The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner
    Alessandro Sorrentino
    Ludwig Institute for Cancer Research, Rudbeck Laboratory, Uppsala University, Sweden, Dag Hammarskjoldsv 20, SE 75185 Uppsala, Sweden
    Nat Cell Biol 10:1199-207. 2008
    ..Our data show that TGF-beta specifically activates TAK1 through interaction of TbetaRI with TRAF6, whereas activation of Smad2 is not dependent on TRAF6...
  82. doi request reprint The LAR protein tyrosine phosphatase enables PDGF β-receptor activation through attenuation of the c-Abl kinase activity
    Wei Zheng
    Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden
    Cell Signal 23:1050-6. 2011
    ..These observations suggest that LAR reduces the basal c-Abl activity thereby allowing for PDGF β-receptor kinase activation...
  83. doi request reprint Erk 5 is necessary for sustained PDGF-induced Akt phosphorylation and inhibition of apoptosis
    Johan Lennartsson
    Ludwig Institute for Cancer Research, Uppsala University, Box 595, SE 751 24, Uppsala, Sweden
    Cell Signal 22:955-60. 2010
    ....
  84. doi request reprint Dynamic control of TGF-beta signaling and its links to the cytoskeleton
    Aristidis Moustakas
    Ludwig Institute for Cancer Research, Uppsala University, P O Box 595, Biomedical Center, SE 751 24 Uppsala, Sweden
    FEBS Lett 582:2051-65. 2008
    ..We discuss mechanisms and models that aim at explaining the coordination between several components of the signaling network downstream of the TGF-beta signal...
  85. pmc Negative regulation of TGFβ signaling by the kinase LKB1 and the scaffolding protein LIP1
    Anita Morén
    Ludwig Institute for Cancer Research, Uppsala University, Box 595, Biomedical Center, Uppsala University, SE 751 24 Uppsala, Sweden
    J Biol Chem 286:341-53. 2011
    ..Accordingly, LKB1 negatively regulates TGFβ gene responses and epithelial-mesenchymal transition. Thus, LKB1 and LIP1 provide negative control of TGFβ signaling...
  86. pmc 2R and remodeling of vertebrate signal transduction engine
    Lukasz Huminiecki
    Ludwig Institute for Cancer Research, Uppsala University, Box 595, SE 751 24 Uppsala, Sweden
    BMC Biol 8:146. 2010
    ..Two rounds of WGD (2R-WGD) occurred at the base of vertebrates, giving rise to an enormous wave of genetic novelty, but a systematic analysis of functional consequences of this event has not yet been performed...
  87. doi request reprint Platelet-derived growth factor-induced signaling pathways interconnect to regulate the temporal pattern of Erk1/2 phosphorylation
    Aleksandra Jurek
    Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden
    Cell Signal 23:280-7. 2011
    ..In conclusion, cross-talk with other PDGFRβ-induced signaling pathways is important for fine-tuning of the pattern of Erk1/2 activation...
  88. ncbi request reprint Mechanisms of TGF-beta signaling in regulation of cell growth and differentiation
    Aristidis Moustakas
    Ludwig Institute for Cancer Research, Uppsala, Sweden
    Immunol Lett 82:85-91. 2002
    ....
  89. doi request reprint Functional role of Meox2 during the epithelial cytostatic response to TGF-beta
    Ulrich Valcourt
    Ludwig Institute for Cancer Research, Uppsala University, Box 595, Biomedical Center, SE 751 24 Uppsala, Sweden
    Mol Oncol 1:55-71. 2007
    ..Thus, Meox2 is primarily involved in the TGF-beta tumor suppressor pathway...
  90. pmc Activation of protein kinase C alpha is necessary for sorting the PDGF beta-receptor to Rab4a-dependent recycling
    Carina Hellberg
    Ludwig Institute for Cancer Research, Uppsala University, Biomedical Center, S 75124 Uppsala, Sweden
    Mol Biol Cell 20:2856-63. 2009
    ....
  91. ncbi request reprint Ecsit-ement on the crossroads of Toll and BMP signal transduction
    Aristidis Moustakas
    Ludwig Institute for Cancer Research, SE 751 24 Uppsala, Sweden
    Genes Dev 17:2855-9. 2003
  92. pmc Platelet-derived growth factor receptor-beta, carrying the activating mutation D849N, accelerates the establishment of B16 melanoma
    Shioto Suzuki
    Ludwig Institute for Cancer Research, Uppsala Branch, Uppsala, Sweden
    BMC Cancer 7:224. 2007
    ..This allowed us to investigate, in an orthotopic tumor model, the role of increased stromal PDGFR-beta signaling in tumor-stroma interactions...
  93. doi request reprint A cis-acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse
    Gerli Rosengren Pielberg
    Department of Medical Biochemistry and Microbiology, Uppsala University, Box 597, SE 751 24 Uppsala, Sweden
    Nat Genet 40:1004-9. 2008
    ..The Gray horse provides a notable example of how humans have cherry-picked mutations with favorable phenotypic effects in domestic animals...
  94. doi request reprint The regulation of TGFbeta signal transduction
    Aristidis Moustakas
    Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden
    Development 136:3699-714. 2009
    ..Signaling is modulated by negative-feedback regulation via inhibitory Smads. We review here the mechanisms of TGFbeta signal transduction in metazoans and emphasize events crucial for embryonic development...
  95. doi request reprint Negative and positive regulation of MAPK phosphatase 3 controls platelet-derived growth factor-induced Erk activation
    Aleksandra Jurek
    Ludwig Institute for Cancer Research, Uppsala University, Box 595, SE 751 24 Uppsala, Sweden
    J Biol Chem 284:4626-34. 2009
    ..In conclusion, MKP3 is an important regulator of PDGF-induced Erk phosphorylation acting in both a rapid positive feed-forward and a later negative feed-back loop...
  96. pmc Nck adapters are involved in the formation of dorsal ruffles, cell migration, and Rho signaling downstream of the platelet-derived growth factor beta receptor
    Aino Ruusala
    Ludwig Institute for Cancer Research, Biomedical Center, Uppsala University, SE 751 24 Uppsala, Sweden
    J Biol Chem 283:30034-44. 2008
    ..Moreover, signaling involving the Rho GTPases was defective in KO cells. In summary, our observations suggest that the Nck adapters are needed for signaling to Rho GTPases and actin dynamics downstream of the PDGFbeta receptor...
  97. doi request reprint A gain-of-function mutation in the PDGFR-beta alters the kinetics of injury response in liver and skin
    Monika Krampert
    Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden
    Lab Invest 88:1204-14. 2008
    ..We confirmed this hypothesis with a second injury model, cutaneous wound healing, where we observed earlier proliferation and formation of granulation tissue in D849N-mutant mice...
  98. ncbi request reprint Development and possible clinical use of antagonists for PDGF and TGF-beta
    Carl Henrik Heldin
    Ludwig Institute for Cancer Research, Box 595, Biomedical Center, S 751 24 Uppsala, Sweden
    Ups J Med Sci 109:165-78. 2004
    ..The present review discusses the development and possible clinical use of antagonsts for PDGF and TGF-beta...
  99. ncbi request reprint New members of the platelet-derived growth factor family of mitogens
    Carl Henrik Heldin
    Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, SE 751 24, Sweden
    Arch Biochem Biophys 398:284-90. 2002
  100. ncbi request reprint A new twist in Smad signaling
    Carl Henrik Heldin
    Ludwig Institute for Cancer Research, Uppsala University, Box 595, SE 751 24 Uppsala, Sweden
    Dev Cell 10:685-6. 2006
    ..New findings demonstrate that transcriptional intermediary factor 1gamma (TIF1gamma) also can bind to R-Smads, as an alternative to Smad4, and mediate different transcriptional effects...
  101. ncbi request reprint Effect of transforming growth factor-beta on calcium homeostasis in prostate carcinoma cells
    Zemfira Z Gizatullina
    Biomedical Center, The Ludwig Institute for Cancer Research, Box 595, SE 751 24 Uppsala, Sweden
    Biochem Biophys Res Commun 304:643-9. 2003
    ..The results implicate that TGF-beta1 affects the function of the mitochondria and may be of significance for the understanding of the proapoptotic effect of TGF-beta1 in these cells...