Johannes L Bos

Summary

Affiliation: University Medical Center Utrecht
Country: The Netherlands

Publications

  1. ncbi request reprint Rap1 signalling: adhering to new models
    J L Bos
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Centre Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Nat Rev Mol Cell Biol 2:369-77. 2001
  2. ncbi request reprint The role of Rap1 in integrin-mediated cell adhesion
    J L Bos
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Biochem Soc Trans 31:83-6. 2003
  3. ncbi request reprint Epac proteins: multi-purpose cAMP targets
    Johannes L Bos
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Trends Biochem Sci 31:680-6. 2006
  4. ncbi request reprint Epac: a new cAMP target and new avenues in cAMP research
    Johannes L Bos
    Department for Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Nat Rev Mol Cell Biol 4:733-8. 2003
  5. pmc Molecular mechanisms in signal transduction and cancer
    Johannes L Bos
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitweg 100 3584 CG, Utrecht, The Netherlands
    EMBO Rep 5:855-9. 2004
  6. ncbi request reprint Linking Rap to cell adhesion
    Johannes L Bos
    Department of Physiological Chemistry and Centre for Biomedical Genetics, UMC Utrecht, Universiteitsweg 100, 3584CG Utrecht, The Netherlands
    Curr Opin Cell Biol 17:123-8. 2005
  7. pmc All in the family? New insights and questions regarding interconnectivity of Ras, Rap1 and Ral
    J L Bos
    Laboratory for Physiological Chemistry and Center for Biomedical Genetics, Utrecht University, Universiteitsweg 100 3584 CG Utrecht, The Netherlands
    EMBO J 17:6776-82. 1998
  8. ncbi request reprint Activation of FoxO transcription factors contributes to the antiproliferative effect of cAMP
    H Bea Kuiperij
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Oncogene 24:2087-95. 2005
  9. pmc Spatial regulation of cyclic AMP-Epac1 signaling in cell adhesion by ERM proteins
    Martijn Gloerich
    Department of Physiological Chemistry, Center for Biomedical Genetics, and Cancer Genomics Center, University Medical Center Utrecht, Utrecht, Netherlands
    Mol Cell Biol 30:5421-31. 2010
  10. doi request reprint The RapGEF PDZ-GEF2 is required for maturation of cell-cell junctions
    Nadia Dubé
    Department of Physiological Chemistry, Centre for Biomedical Genetics and Cancer Genomics Centre, Utrecht, The Netherlands
    Cell Signal 20:1608-15. 2008

Collaborators

Detail Information

Publications74

  1. ncbi request reprint Rap1 signalling: adhering to new models
    J L Bos
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Centre Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Nat Rev Mol Cell Biol 2:369-77. 2001
    ....
  2. ncbi request reprint The role of Rap1 in integrin-mediated cell adhesion
    J L Bos
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Biochem Soc Trans 31:83-6. 2003
    ..From these results, we conclude that one of the functions of receptor-induced Rap1 activation is inside-out regulation of integrins...
  3. ncbi request reprint Epac proteins: multi-purpose cAMP targets
    Johannes L Bos
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Trends Biochem Sci 31:680-6. 2006
    ..In most of these processes, cAMP signaling through protein kinase A (PKA) is also involved, stressing the interconnectivity between Epac- and PKA-mediated signaling...
  4. ncbi request reprint Epac: a new cAMP target and new avenues in cAMP research
    Johannes L Bos
    Department for Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Nat Rev Mol Cell Biol 4:733-8. 2003
    ..Structural analysis of the cAMP-binding domains of Epac2 has identified a unifying mechanism for how cAMP activates proteins, and the design and synthesis of an Epac-specific cAMP analogue has paved the way for future discoveries...
  5. pmc Molecular mechanisms in signal transduction and cancer
    Johannes L Bos
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitweg 100 3584 CG, Utrecht, The Netherlands
    EMBO Rep 5:855-9. 2004
  6. ncbi request reprint Linking Rap to cell adhesion
    Johannes L Bos
    Department of Physiological Chemistry and Centre for Biomedical Genetics, UMC Utrecht, Universiteitsweg 100, 3584CG Utrecht, The Netherlands
    Curr Opin Cell Biol 17:123-8. 2005
    ..Recently, several effector proteins for Rap1 have been identified providing a clear link between Rap1 and actin dynamics. Furthermore, evidence is accumulating that Rap1 functions in the spatial and temporal control of cell polarity...
  7. pmc All in the family? New insights and questions regarding interconnectivity of Ras, Rap1 and Ral
    J L Bos
    Laboratory for Physiological Chemistry and Center for Biomedical Genetics, Utrecht University, Universiteitsweg 100 3584 CG Utrecht, The Netherlands
    EMBO J 17:6776-82. 1998
    ..Here, I summarize the recent developments in understanding the functional relationship between these three GTPase and argue that Rap1 functions in a signalling pathway distinct from Ras, while using similar or identical effectors...
  8. ncbi request reprint Activation of FoxO transcription factors contributes to the antiproliferative effect of cAMP
    H Bea Kuiperij
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Oncogene 24:2087-95. 2005
    ..From these results we conclude that inhibition of PKB and subsequent activation of FoxO transcription factors mediates an antiproliferative effect of cAMP...
  9. pmc Spatial regulation of cyclic AMP-Epac1 signaling in cell adhesion by ERM proteins
    Martijn Gloerich
    Department of Physiological Chemistry, Center for Biomedical Genetics, and Cancer Genomics Center, University Medical Center Utrecht, Utrecht, Netherlands
    Mol Cell Biol 30:5421-31. 2010
    ..We conclude that ERM proteins are involved in the spatial regulation of Epac1 and cooperate with cAMP- and Rap-mediated signaling to regulate adhesion to the extracellular matrix...
  10. doi request reprint The RapGEF PDZ-GEF2 is required for maturation of cell-cell junctions
    Nadia Dubé
    Department of Physiological Chemistry, Centre for Biomedical Genetics and Cancer Genomics Centre, Utrecht, The Netherlands
    Cell Signal 20:1608-15. 2008
    ..Our results present the first direct evidence that PDZ-GEF2 plays a critical role in the maturation of adherens junctions...
  11. doi request reprint Structure of Epac2 in complex with a cyclic AMP analogue and RAP1B
    Holger Rehmann
    Department of Physiological Chemistry, Centre for Biomedical Genetics and Cancer Genomics Centre, University Medical Center, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Nature 455:124-7. 2008
    ....
  12. pmc Cyclic AMP induces integrin-mediated cell adhesion through Epac and Rap1 upon stimulation of the beta 2-adrenergic receptor
    Savithri Rangarajan
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Netherlands
    J Cell Biol 160:487-93. 2003
    ..From these results we conclude that cAMP mediates receptor-induced integrin-mediated cell adhesion to fibronectin through the Epac-Rap1 signaling pathway...
  13. doi request reprint Ezrin is required for efficient Rap1-induced cell spreading
    Sarah H Ross
    Molecular Cancer Research, Centre for Biomedical Genetics and Cancer Genomics Centre, University Medical Centre Utrecht, 3584 CG Utrecht, The Netherlands
    J Cell Sci 124:1808-18. 2011
    ..Here, we present a novel function for Ezrin in Rap1-induced cell spreading and evidence of a non-redundant role of an ERM family member...
  14. pmc Rap1 can bypass the FAK-Src-Paxillin cascade to induce cell spreading and focal adhesion formation
    Sarah H Ross
    Department of Molecular Cancer Research, Centre for Biomedical Genetics and Cancer Genomics Centre, University Medical Center, Utrecht, The Netherlands
    PLoS ONE 7:e50072. 2012
    ..From these results, we conclude that Rap1 can induce cell adhesion and stimulate an accelerated rate of cell spreading through mechanisms that bypass the canonical FAK-Src-Paxillin signalling cascade...
  15. ncbi request reprint Ligand-mediated activation of the cAMP-responsive guanine nucleotide exchange factor Epac
    Holger Rehmann
    Department of Physiological Chemistry and Centre of Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    J Biol Chem 278:38548-56. 2003
    ....
  16. doi request reprint Epac1 and PDZ-GEF cooperate in Rap1 mediated endothelial junction control
    Willem Jan Pannekoek
    Molecular Cancer Research, Centre of Biomedical Genetics and Cancer Genomics Centre, University Medical Center Utrecht, Utrecht, The Netherlands
    Cell Signal 23:2056-64. 2011
    ..We conclude that PDZ-GEF activates Rap1 under resting conditions to stabilize cell-cell junctions and maintain basal integrity. Activation of Rap1 by cAMP/Epac1 induces junctional actin to further tighten cell-cell contacts...
  17. pmc cAMP regulates DEP domain-mediated binding of the guanine nucleotide exchange factor Epac1 to phosphatidic acid at the plasma membrane
    Sarah V Consonni
    Molecular Cancer Research, University Medical Center Utrecht, 3584 CG, Utrecht, The Netherlands
    Proc Natl Acad Sci U S A 109:3814-9. 2012
    ..From these results we conclude that cAMP induces a conformational change in Epac1 that enables DEP domain-mediated binding to phosphatidic acid, resulting in the tethering of Epac1 at the plasma membrane and subsequent activation of Rap...
  18. ncbi request reprint The small GTPase Rap1 is activated by turbulence and is involved in integrin [alpha]IIb[beta]3-mediated cell adhesion in human megakaryocytes
    Kim M T de Bruyn
    Department of Physiological Chemistry, University Medical Center, Utrecht, The Netherlands
    J Biol Chem 278:22412-7. 2003
    ..From these results we conclude that in megakaryocytes turbulence induces Rap1 activation that controls alphaIIbbeta3-mediated cell adhesion...
  19. pmc FOXO transcription factor activation by oxidative stress mediated by the small GTPase Ral and JNK
    Marieke A G Essers
    Department of Physiological Chemistry, Centre for Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
    EMBO J 23:4802-12. 2004
    ..The results reported here, therefore, outline a homeostasis mechanism for sustaining cellular reactive oxygen species that is controlled by signalling pathways that can convey both negative (PI-3K/PKB) and positive (Ras/Ral) inputs...
  20. doi request reprint Quantitative global phosphoproteomics of human umbilical vein endothelial cells after activation of the Rap signaling pathway
    Lars A T Meijer
    Molecular Cancer Research, Centre for Biomedical Genetics and Cancer Genomics Centre, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Mol Biosyst 9:732-49. 2013
    ..Compatible with the function of Rap1, these alterations were found predominantly in proteins regulating the actin cytoskeleton, cell-cell junctions and cell adhesion...
  21. doi request reprint cAMP-induced Epac-Rap activation inhibits epithelial cell migration by modulating focal adhesion and leading edge dynamics
    Karen S Lyle
    Department of Physiological Chemistry, Centre for Biomedical Genetics and Cancer Genomics Centre, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Cell Signal 20:1104-16. 2008
    ..This extends beyond the effect of integrin affinity modulation and argues for an additional function of Rap in controlling the migration machinery of epithelial cells...
  22. pmc The nucleoporin RanBP2 tethers the cAMP effector Epac1 and inhibits its catalytic activity
    Martijn Gloerich
    Molecular Cancer Research, Centre for Biomedical Genetics and Cancer Genomics Centre, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands
    J Cell Biol 193:1009-20. 2011
    ..These results reveal a novel mechanism of Epac1 regulation and elucidate an unexpected link between the NPC and cAMP signaling...
  23. doi request reprint Rap2A links intestinal cell polarity to brush border formation
    Martijn Gloerich
    Molecular Cancer Research, Centre for Biomedical Genetics and Cancer Genomics Centre, University Medical Center Utrecht, Utrecht 3584 CG, The Netherlands
    Nat Cell Biol 14:793-801. 2012
    ..Thus, epithelial cell polarization is translated directly into the acquisition of brush borders through a small G protein signalling module whose action is positioned by a cortical lipid cue...
  24. pmc Evolution of the TOR pathway
    Teunis J P van Dam
    Theoretical Biology and Bioinformatics, Department of Biology, Science Faculty, Utrecht University, Padualaan 8, Utrecht, The Netherlands
    J Mol Evol 73:209-20. 2011
    ..In yeast we identify novel AGC kinases that are orthologous to the S6 kinase. These results demonstrate how a vital signaling pathway can be both highly conserved and flexible in eukaryotes...
  25. ncbi request reprint Structure of the cyclic-AMP-responsive exchange factor Epac2 in its auto-inhibited state
    Holger Rehmann
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Nature 439:625-8. 2006
    ..Mutational analysis suggests a model for cAMP-induced Epac activation with rigid body movement of the regulatory region, the features of which are universally conserved in cAMP-regulated proteins...
  26. ncbi request reprint Pull-down assays for guanoside 5'-triphosphate-bound Ras-like guanosine 5'-triphosphatases
    Miranda van Triest
    Department of Physiological Chemistry, Centre for Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
    Methods Mol Biol 250:97-102. 2004
  27. ncbi request reprint Rap1 regulates E-cadherin-mediated cell-cell adhesion
    Leo S Price
    Department of Physiological Chemistry and the Centre for Biomedical Genetics, University Medical Centre Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    J Biol Chem 279:35127-32. 2004
    ..Our results imply that Rap may function in a broader manner to regulate the function of cell-surface adhesion receptors...
  28. ncbi request reprint A novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK
    Jorrit M Enserink
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584CG Utrecht, The Netherlands
    Nat Cell Biol 4:901-6. 2002
    ..Moreover, in cell lines in which cAMP activates ERK, inhibition of PKA and Ras, but not Rap1, abolished cAMP-mediated ERK activation. We conclude that cAMP-induced regulation of ERK and activation of Rap1 are independent processes...
  29. pmc Down-regulation of Rap1 activity is involved in ephrinB1-induced cell contraction
    Jurgen A Riedl
    Department of Physiological Chemistry, Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Biochem J 389:465-9. 2005
    ..From these results, we conclude that down-regulation of Rap1 is a prerequisite for ephrin-induced cell retraction in colon cells...
  30. doi request reprint Cell-cell junction formation: the role of Rap1 and Rap1 guanine nucleotide exchange factors
    Willem Jan Pannekoek
    Department of Physiological Chemistry, Centre for Biomedical Genetics and Cancer Genomics Centre, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Biochim Biophys Acta 1788:790-6. 2009
    ..In this review, we will highlight the latest findings on the Rap signaling network in the control of epithelial and endothelial cell-cell junctions...
  31. ncbi request reprint Regulation of sterol carrier protein gene expression by the forkhead transcription factor FOXO3a
    Tobias B Dansen
    Department of Biochemistry of Lipids, Institute of Biomembranes, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands
    J Lipid Res 45:81-8. 2004
    ..We propose a model for the way in which SCP2 could protect fatty acids from peroxidation...
  32. ncbi request reprint Characterisation of PDZ-GEFs, a family of guanine nucleotide exchange factors specific for Rap1 and Rap2
    H Bea Kuiperij
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Centre Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands
    Biochim Biophys Acta 1593:141-9. 2003
    ..We conclude that both PDZ-GEF1 and 2 are specific for Rap1 and Rap2 and unresponsive to cAMP and various other nucleotides...
  33. pmc Rap1 and Rap2 antagonistically control endothelial barrier resistance
    Willem Jan Pannekoek
    Molecular Cancer Research, University Medical Center Utrecht, Utrecht, The Netherlands
    PLoS ONE 8:e57903. 2013
    ..This Rap1-antagonizing effect of Rap2 is established independent of junctional actin formation. These data establish that endothelial barrier resistance is determined by the combined antagonistic actions of Rap1 and Rap2...
  34. ncbi request reprint Epac1 regulates integrity of endothelial cell junctions through VE-cadherin
    Matthijs R H Kooistra
    Department of Physiological Chemistry, Centre for Biomedical Genetics, University Medical Center, Utrecht, The Netherlands
    FEBS Lett 579:4966-72. 2005
    ..From these results we conclude that in human umbilical vein endothelial cells Epac1 controls VE-cadherin-mediated cell junction formation and induces reorganization of the actin cytoskeleton...
  35. pmc Specificity in Ras and Rap signaling
    Judith H Raaijmakers
    Department of Physiological Chemistry, Centre for Biomedical Genetics, Universitair Medisch Centrum Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    J Biol Chem 284:10995-9. 2009
    ..In this review, we discuss the regulatory proteins and effectors of Ras and Rap, with a focus on those of Rap...
  36. ncbi request reprint Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress
    Geert J P L Kops
    Department of Physiological Chemistry, University Medical Center Utrecht and Center for Biomedical Genetics, 3584 CG Utrecht, The Netherlands
    Nature 419:316-21. 2002
    ..The model of Forkhead involvement in regulating longevity stems from genetic analysis in Caenorhabditis elegans, and we conclude that this model also extends to mammalian systems...
  37. pmc Rasip1 mediates Rap1 regulation of Rho in endothelial barrier function through ArhGAP29
    Anneke Post
    Molecular Cancer Research, University Medical Center Utrecht, 3582 CG Utrecht, The Netherlands
    Proc Natl Acad Sci U S A 110:11427-32. 2013
    ..These results reveal an effector pathway for Rap1 in the modulation of Rho signaling and actin dynamics, through which Rap1 modulates endothelial barrier function. ..
  38. ncbi request reprint Communication between the regulatory and the catalytic region of the cAMP-responsive guanine nucleotide exchange factor Epac
    Holger Rehmann
    Department of Physiological Chemistry and Centre of Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    J Biol Chem 278:23508-14. 2003
    ..From these results we conclude that the LID region plays a pivotal role in the communication between the regulatory and catalytic part of Epac...
  39. ncbi request reprint GEFs and GAPs: critical elements in the control of small G proteins
    Johannes L Bos
    Department of Physiological Chemistry and Centre of Biomedical Genetics, UMC Utrecht Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Cell 129:865-77. 2007
    ..Recent evidence suggests that these proteins may be potential therapeutic targets for developing drugs to treat various diseases, including cancer...
  40. pmc RAP-1 and the RAL-1/exocyst pathway coordinate hypodermal cell organization in Caenorhabditis elegans
    Ester W Frische
    Department of Physiological Chemistry, Centre for Biomedical Genetics, UMC Utrecht, Utrecht, The Netherlands
    EMBO J 26:5083-92. 2007
    ..Genetic interactions show that the RAP-1 and RAL-1/exocyst pathway also act in parallel during larval stages. Together these data provide in vivo evidence for the exocyst complex as a downstream RAL-1 effector in cell migration...
  41. doi request reprint Structural dynamics in the activation of Epac
    Shannon M Harper
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
    J Biol Chem 283:6501-8. 2008
    ..The results reveal the critical elements of the CNB domain of Epac required for activation and highlight the role of dynamics in this process...
  42. doi request reprint Epac: defining a new mechanism for cAMP action
    Martijn Gloerich
    Department of Physiological Chemistry, University Medical Center, Utrecht, The Netherlands
    Annu Rev Pharmacol Toxicol 50:355-75. 2010
    ..Advances in the understanding of the activation mechanism of Epac and its regulation by diverse anchoring mechanisms have helped to elucidate the means by which cAMP fulfills these functions via Epac...
  43. doi request reprint Phylogeny of the CDC25 homology domain reveals rapid differentiation of Ras pathways between early animals and fungi
    Teunis J P van Dam
    Theoretical Biology and Bioinformatics, Department of Biology, Science Faculty, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands
    Cell Signal 21:1579-85. 2009
    ..Finally, a comparison of the domain composition of the Ras guanine nucleotide exchange factors shows that domain addition and diversification occurred both prior to and after the fungal-animal split...
  44. ncbi request reprint The PI3K effector Arap3 interacts with the PI(3,4,5)P3 phosphatase SHIP2 in a SAM domain-dependent manner
    Judith H Raaijmakers
    Department of Physiological Chemistry and Centre of Biomedical Genetics, UMC Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Cell Signal 19:1249-57. 2007
    ..Since it was shown previously that Arap3 has a higher affinity for PI(3,4,5,)P3 than for PI(3,4)P2, we propose that the SAM domain of Arap3 can function to recruit a negative regulator of PI3K signaling into the effector complex...
  45. pmc Regulation of the Forkhead transcription factor AFX by Ral-dependent phosphorylation of threonines 447 and 451
    N D De Ruiter
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands
    Mol Cell Biol 21:8225-35. 2001
    ....
  46. ncbi request reprint AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1
    R H Medema
    Department of Hematology, University Medical Center, Utrecht, The Netherlands
    Nature 404:782-7. 2000
    ..We conclude that AFX-like proteins are involved in cell-cycle regulation and that inactivation of these proteins is an important step in oncogenic transformation...
  47. pmc Distinct regulation of p53 and p73 activity by adenovirus E1A, E1B, and E4orf6 proteins
    W T Steegenga
    Laboratory for Physiological Chemistry and Centre for Biomedical Genetics, Utrecht University, 3508 TA Utrecht, The Netherlands
    Mol Cell Biol 19:3885-94. 1999
    ..Our results suggest that the p53 and p73 proteins are both inactivated after Ad infection and transformation but via distinct mechanisms...
  48. doi request reprint Regulating Rap small G-proteins in time and space
    Martijn Gloerich
    Molecular Cancer Research, Centre for Biomedical Genetics and Cancer Genomics Centre, University Medical Center Utrecht, Utrecht, The Netherlands
    Trends Cell Biol 21:615-23. 2011
    ..Here, we review the various activating signals and targeting mechanisms of these proteins and discuss their contribution to the spatiotemporal regulation and biological functions of the Rap proteins...
  49. ncbi request reprint Capturing cyclic nucleotides in action: snapshots from crystallographic studies
    Holger Rehmann
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Nat Rev Mol Cell Biol 8:63-73. 2007
    ..Recent structural insights have now made it possible to propose a general structural mechanism for how cyclic nucleotides regulate these proteins...
  50. ncbi request reprint Rap1: a key regulator in cell-cell junction formation
    Matthijs R H Kooistra
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    J Cell Sci 120:17-22. 2007
    ..These findings point to a role of Rap1 in spatial and temporal control of cell-cell junction formation...
  51. ncbi request reprint Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP
    J de Rooij
    Laboratory for Physiological Chemistry and Centre for Biomedical Genetics, Utrecht University, The Netherlands
    Nature 396:474-7. 1998
    ..cAMP strongly induces the GEF activity of Epac towards Rap1 both in vivo and in vitro. We conclude that Epac is a GEF for Rap1 that is regulated directly by cAMP and that Epac is a new target protein for cAMP...
  52. ncbi request reprint RalGDS-like factor (Rlf) is a novel Ras and Rap 1A-associating protein
    R M Wolthuis
    Laboratory for Physiological Chemistry, Utrecht University, The Netherlands
    Oncogene 13:353-62. 1996
    ..6 microM and 0.4 microM, respectively. No significant association with Ras-GDP or Rap 1A-GDP could be detected. These binding characteristics indicate that Rlf is a putative effector for Ras and Rap 1A...
  53. ncbi request reprint Mechanism of regulation of the Epac family of cAMP-dependent RapGEFs
    J de Rooij
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Centre Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    J Biol Chem 275:20829-36. 2000
    ..Epac1 becomes activated by a release of this inhibition when cAMP is bound...
  54. doi request reprint Semaphorin signaling meets rap
    Johannes L Bos
    Molecular Cancer Research, Centre of Biomedical Genetics and Cancer Genomics Centre, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, Netherlands
    Sci Signal 5:pe6. 2012
    ..This important finding connects semaphorin signaling to Rap-mediated signaling and is another intriguing example of how small GTPases are used for spatial and temporal control of cell behavior...
  55. ncbi request reprint The small GTPase Rap1 is required for Mn(2+)- and antibody-induced LFA-1- and VLA-4-mediated cell adhesion
    Kim M T de Bruyn
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Centre Utrecht, Utrecht University, Universiteitsweg 100, P O Box 85060, 3508 AB Utrecht, The Netherlands
    J Biol Chem 277:29468-76. 2002
    ..We suggest that Rap1 determines the functional availability of integrins for productive binding to integrin ligands...
  56. ncbi request reprint PDZ-GEF1, a guanine nucleotide exchange factor specific for Rap1 and Rap2
    J de Rooij
    Laboratory for Physiological Chemistry, Center for Biomedical Genetics, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    J Biol Chem 274:38125-30. 1999
    ..This is the first example of an exchange factor acting on Rap2. We conclude that PDZ-GEF1 is a guanine nucleotide exchange factor, specific for Rap1 and Rap2, that is controlled by a negative regulatory domain...
  57. pmc Requirement of the Caenorhabditis elegans RapGEF pxf-1 and rap-1 for epithelial integrity
    W Pellis-van Berkel
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands
    Mol Biol Cell 16:106-16. 2005
    ..Together these results demonstrate that the pxf-1/rap pathway in C. elegans is required for maintenance of epithelial integrity, in which it probably functions in polarized secretion...
  58. pmc Rab5 induces Rac-independent lamellipodia formation and cell migration
    M Spaargaren
    Laboratory for Physiological Chemistry, Utrecht University, 3584 CG Utrecht, The Netherlands
    Mol Biol Cell 10:3239-50. 1999
    ..Thus, Rab5 can control not only endocytosis but also actin cytoskeleton reorganization and cell migration, which provides strong support for an intricate relationship between these processes...
  59. ncbi request reprint RalGEF2, a pleckstrin homology domain containing guanine nucleotide exchange factor for Ral
    K M de Bruyn
    Department of Physiological Chemistry, University Medical Centre Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    J Biol Chem 275:29761-6. 2000
    ....
  60. ncbi request reprint Regulation of the small GTPase Rheb by amino acids
    M Roccio
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands
    Oncogene 25:657-64. 2006
    ..Since under these conditions Rheb-GTP levels remain high, a second level of amino-acid sensing exists, affecting mTOR activity in a Rheb-independent fashion...
  61. ncbi request reprint AF6 negatively regulates Rap1-induced cell adhesion
    Zhongchun Zhang
    Department of Physiological Chemistry and Centre of Biomedical Genetics, University Medical Centre, Utrecht 3508 AB, The Netherlands
    J Biol Chem 280:33200-5. 2005
    ..Thus, AF6 may buffer RapGTP in resting T cells and maintain them in a non-adherent state...
  62. pmc Detecting cAMP-induced Epac activation by fluorescence resonance energy transfer: Epac as a novel cAMP indicator
    Bas Ponsioen
    Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands
    EMBO Rep 5:1176-80. 2004
    ..These properties make Epac-based FRET probes the preferred indicators for monitoring cAMP levels in vivo...
  63. ncbi request reprint The cAMP-Epac-Rap1 pathway regulates cell spreading and cell adhesion to laminin-5 through the alpha3beta1 integrin but not the alpha6beta4 integrin
    Jorrit M Enserink
    Biotechnology Centre of Oslo, University of Oslo, Blindern, N 0317 Oslo, Norway
    J Biol Chem 279:44889-96. 2004
    ..They also define different roles for the laminin-binding integrins in regulated cell adhesion and subsequent cell spreading...
  64. ncbi request reprint Structure and regulation of the cAMP-binding domains of Epac2
    Holger Rehmann
    Max Planck Institut fur molekulare Physiologie, Otto Hahn Strasse 11, D 44227, Dortmund, Germany
    Nat Struct Biol 10:26-32. 2003
    ..We identify a hinge region that couples cAMP binding to a conformational change of the C-terminal regions. Mutations in the hinge of Epac can uncouple cAMP binding from its exchange activity...
  65. ncbi request reprint cAMP analog mapping of Epac1 and cAMP kinase. Discriminating analogs demonstrate that Epac and cAMP kinase act synergistically to promote PC-12 cell neurite extension
    Anne E Christensen
    Department of Anatomy and Cell Biology, University of Bergen, 5009 Bergen, Norway
    J Biol Chem 278:35394-402. 2003
    ..We therefore conclude that cAMP-induced neurite outgrowth is mediated by both Epac and cAPK...
  66. pmc Growth factors can activate ATF2 via a two-step mechanism: phosphorylation of Thr71 through the Ras-MEK-ERK pathway and of Thr69 through RalGDS-Src-p38
    D Margriet Ouwens
    Department of Molecular Cell Biology, Section of Signal Transduction, Leiden University Medical Centre, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands
    EMBO J 21:3782-93. 2002
    ..These results reveal a so far unknown mechanism by which distinct MAPK pathways and Ras effector pathways cooperate to activate a transcription factor...
  67. ncbi request reprint Signal transduction: thumbs up for inactivation
    Holger Rehmann
    Nature 429:138-9. 2004
  68. ncbi request reprint Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2
    Attila Garami
    Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland
    Mol Cell 11:1457-66. 2003
    ..Finally, coexpression of a human TSC2 cDNA harboring a disease-associated point mutation in the GAP domain, failed to stimulate Rheb GTPase activity or block Rheb activation of S6K1...
  69. pmc cAMP sensor Epac as a determinant of ATP-sensitive potassium channel activity in human pancreatic beta cells and rat INS-1 cells
    Guoxin Kang
    Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY, USA
    J Physiol 573:595-609. 2006
    ....
  70. doi request reprint Cyclic nucleotide analogs as probes of signaling pathways
    Heiko Poppe
    Nat Methods 5:277-8. 2008
  71. ncbi request reprint Rap1 signaling is required for suppression of Ras-generated reactive oxygen species and protection against oxidative stress in T lymphocytes
    Philip H J Remans
    Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    J Immunol 173:920-31. 2004
    ..Introduction of dominant-negative Ras into synovial fluid T cells restored redox balance, providing evidence that deregulated Ras and Rap1 signaling underlies oxidative stress and consequent altered T cell function observed in RA...
  72. ncbi request reprint RAPL: taking the Rap in immunity
    Leo S Price
    Nat Immunol 5:1007-8. 2004
  73. pmc Epac-selective cAMP analog 8-pCPT-2'-O-Me-cAMP as a stimulus for Ca2+-induced Ca2+ release and exocytosis in pancreatic beta-cells
    Guoxin Kang
    Department of Physiology and Neuroscience, New York University School of Medicine, New York 10016, USA
    J Biol Chem 278:8279-85. 2003
    ....
  74. pmc Exchange protein activated by cAMP (Epac) mediates cAMP activation of p38 MAPK and modulation of Ca2+-dependent K+ channels in cerebellar neurons
    Jeanne Ster
    Institute of Functional Genomics, Centre National de la Recherche Scientifique, Unite Mixte de Recherche 5203, Institute National de la Santé et de la Recherche Médicale U661, Universites Montpellier I et II, 34095 Montpellier, France
    Proc Natl Acad Sci U S A 104:2519-24. 2007
    ..These effects involve activation of Rap and p38 MAPK, which mobilizes intracellular Ca2+ stores. These findings reveal a cAMP Epac-dependent and protein kinase A-independent signaling cascade that controls neuronal excitability...