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Volumn 17, Issue 2, 2005, Pages 129-134

Arrestin times for compartmentalised cAMP signalling and phosphodiesterase-4 enzymes

Author keywords

[No Author keywords available]

Indexed keywords

BETA 2 ADRENERGIC RECEPTOR; BETA ARRESTIN; CD28 ANTIGEN; CYCLIC AMP; CYCLIC AMP DEPENDENT PROTEIN KINASE; ISOENZYME; PHOSPHODIESTERASE IV; RETINA S ANTIGEN; T LYMPHOCYTE RECEPTOR;

EID: 15044353649     PISSN: 09550674     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ceb.2005.01.003     Document Type: Review
Times cited : (117)

References (44)
  • 1
    • 0036729478 scopus 로고    scopus 로고
    • Cyclic nucleotide research - Still expanding after half a century
    • J.A. Beavo, and L.L. Brunton Cyclic nucleotide research - still expanding after half a century Nat Rev Mol Cell Biol 3 2002 710 718
    • (2002) Nat Rev Mol Cell Biol , vol.3 , pp. 710-718
    • Beavo, J.A.1    Brunton, L.L.2
  • 2
    • 0347359224 scopus 로고    scopus 로고
    • Localized effects of cAMP mediated by distinct routes of protein kinase a
    • K. Tasken, and E.M. Aandahl Localized effects of cAMP mediated by distinct routes of protein kinase A Physiol Rev 84 2004 137 167
    • (2004) Physiol Rev , vol.84 , pp. 137-167
    • Tasken, K.1    Aandahl, E.M.2
  • 3
    • 0019349003 scopus 로고
    • Functional compartmentation of cyclic AMP and protein kinase in heart
    • L.L. Brunton, J.S. Hayes, and S.E. Mayer Functional compartmentation of cyclic AMP and protein kinase in heart Adv Cyclic Nucleotide Res 14 1981 391 397
    • (1981) Adv Cyclic Nucleotide Res , vol.14 , pp. 391-397
    • Brunton, L.L.1    Hayes, J.S.2    Mayer, S.E.3
  • 4
    • 0036500494 scopus 로고    scopus 로고
    • Discrete microdomains with high concentration of cAMP in stimulated rat neonatal cardiac myocytes
    • M. Zaccolo, and T. Pozzan Discrete microdomains with high concentration of cAMP in stimulated rat neonatal cardiac myocytes Science 295 2002 1711 1715
    • (2002) Science , vol.295 , pp. 1711-1715
    • Zaccolo, M.1    Pozzan, T.2
  • 5
    • 0035910074 scopus 로고    scopus 로고
    • Genetically encoded reporters of protein kinase a activity reveal impact of substrate tethering
    • J. Zhang, Y. Ma, S.S. Taylor, and R.Y. Tsien Genetically encoded reporters of protein kinase A activity reveal impact of substrate tethering Proc Natl Acad Sci USA 98 2001 14997 15002
    • (2001) Proc Natl Acad Sci USA , vol.98 , pp. 14997-15002
    • Zhang, J.1    Ma, Y.2    Taylor, S.S.3    Tsien, R.Y.4
  • 7
    • 0041836339 scopus 로고    scopus 로고
    • EPAC: A new cAMP target and new avenues in cAMP research
    • J.L. Bos EPAC: a new cAMP target and new avenues in cAMP research Nat Rev Mol Cell Biol 4 2003 733 738 This study reviews a new molecule, EPAC, that provides an output, alongside PKA, for cAMP signalling.
    • (2003) Nat Rev Mol Cell Biol , vol.4 , pp. 733-738
    • Bos, J.L.1
  • 8
    • 4444377903 scopus 로고    scopus 로고
    • Novel single chain cAMP sensors for receptor-induced signal propagation
    • V.O. Nikolaev, M. Bunemann, L. Hein, A. Hannawacker, and M.J. Lohse Novel single chain cAMP sensors for receptor-induced signal propagation J Biol Chem 279 2004 37215 37218 This study shows how EPACs can be modified to generate a FRET probe for reporting on changes in cAMP in living cells.
    • (2004) J Biol Chem , vol.279 , pp. 37215-37218
    • Nikolaev, V.O.1    Bunemann, M.2    Hein, L.3    Hannawacker, A.4    Lohse, M.J.5
  • 9
    • 10644280705 scopus 로고    scopus 로고
    • Negative feedback exerted by PKA and cAMP phosphodiesterase on subsarcolemmal cAMP signals in Intact cardiac myocytes. An in vivo study using adenovirus-mediated expression of CNG channels
    • F. Rochais, G. Vandecasteele, F. Lefebvre, C. Lugnier, H. Lum, J.L. Mazet, D.M. Cooper, and R. Fischmeister Negative feedback exerted by PKA and cAMP phosphodiesterase on subsarcolemmal cAMP signals in Intact cardiac myocytes. An in vivo study using adenovirus-mediated expression of CNG channels J Biol Chem 279 2004 52095 52105 This study provides a demonstration that a cyclic-nucleotide-gated ion channel can be used to report on compartmentalised cAMP changes in cardiac myocytes.
    • (2004) J Biol Chem , vol.279 , pp. 52095-52105
    • Rochais, F.1    Vandecasteele, G.2    Lefebvre, F.3    Lugnier, C.4    Lum, H.5    Mazet, J.L.6    Cooper, D.M.7    Fischmeister, R.8
  • 11
  • 13
    • 0032723853 scopus 로고    scopus 로고
    • Cyclic nucleotide phosphodiesterases (PDEs): Diverse regulators of cyclic nucleotide signals and inviting molecular targets for novel therapeutic agents
    • V.C. Manganiello, and E. Degerman Cyclic nucleotide phosphodiesterases (PDEs): diverse regulators of cyclic nucleotide signals and inviting molecular targets for novel therapeutic agents Thromb Haemost 82 1999 407 411
    • (1999) Thromb Haemost , vol.82 , pp. 407-411
    • Manganiello, V.C.1    Degerman, E.2
  • 14
    • 0037443097 scopus 로고    scopus 로고
    • PDE4 cAMP phosphodiesterases: Modular enzymes that orchestrate signalling cross-talk, desensitization and compartmentalization
    • M.D. Houslay, and D.R. Adams PDE4 cAMP phosphodiesterases: modular enzymes that orchestrate signalling cross-talk, desensitization and compartmentalization Biochem J 370 2003 1 18
    • (2003) Biochem J , vol.370 , pp. 1-18
    • Houslay, M.D.1    Adams, D.R.2
  • 15
    • 0035224418 scopus 로고    scopus 로고
    • PDE4 cAMP-specific phosphodiesterases
    • M.D. Houslay PDE4 cAMP-specific phosphodiesterases Prog Nucleic Acid Res Mol Biol 69 2001 249 315
    • (2001) Prog Nucleic Acid Res Mol Biol , vol.69 , pp. 249-315
    • Houslay, M.D.1
  • 16
    • 0037458648 scopus 로고    scopus 로고
    • Cyclic AMP-specific PDE4 phosphodiesterases as critical components of cyclic AMP signaling
    • M. Conti, W. Richter, C. Mehats, G. Livera, J.Y. Park, and C. Jin Cyclic AMP-specific PDE4 phosphodiesterases as critical components of cyclic AMP signaling J Biol Chem 278 2003 5493 5496
    • (2003) J Biol Chem , vol.278 , pp. 5493-5496
    • Conti, M.1    Richter, W.2    Mehats, C.3    Livera, G.4    Park, J.Y.5    Jin, C.6
  • 17
    • 0033818504 scopus 로고    scopus 로고
    • New phosphodiesterase inhibitors as therapeutics for the treatment of chronic lung disease
    • M.S. Barnette, and D.C. Underwood New phosphodiesterase inhibitors as therapeutics for the treatment of chronic lung disease Curr Opin Pulm Med 6 2000 164 169
    • (2000) Curr Opin Pulm Med , vol.6 , pp. 164-169
    • Barnette, M.S.1    Underwood, D.C.2
  • 18
    • 0344513958 scopus 로고    scopus 로고
    • Phosphodiesterase-4 inhibitors in the treatment of inflammatory lung disease
    • D. Spina Phosphodiesterase-4 inhibitors in the treatment of inflammatory lung disease Drugs 63 2003 2575 2594
    • (2003) Drugs , vol.63 , pp. 2575-2594
    • Spina, D.1
  • 19
    • 0036790883 scopus 로고    scopus 로고
    • Antidepressant-like profile and reduced sensitivity to rolipram in mice deficient in the PDE4D phosphodiesterase enzyme
    • H.T. Zhang, Y. Huang, S.L. Jin, S.A. Frith, N. Suvarna, M. Conti, and J.M. O'Donnell Antidepressant-like profile and reduced sensitivity to rolipram in mice deficient in the PDE4D phosphodiesterase enzyme Neuropsychopharmacology 27 2002 587 595
    • (2002) Neuropsychopharmacology , vol.27 , pp. 587-595
    • Zhang, H.T.1    Huang, Y.2    Jin, S.L.3    Frith, S.A.4    Suvarna, N.5    Conti, M.6    O'Donnell, J.M.7
  • 20
    • 0037188511 scopus 로고    scopus 로고
    • Induction of the cyclic nucleotide phosphodiesterase PDE4B is essential for LPS-activated TNF-alpha responses
    • S.L. Jin, and M. Conti Induction of the cyclic nucleotide phosphodiesterase PDE4B is essential for LPS-activated TNF-alpha responses Proc Natl Acad Sci USA 99 2002 7628 7633
    • (2002) Proc Natl Acad Sci USA , vol.99 , pp. 7628-7633
    • Jin, S.L.1    Conti, M.2
  • 21
    • 0141445980 scopus 로고    scopus 로고
    • PDE4D plays a critical role in the control of airway smooth muscle contraction
    • C. Mehats, S.L. Jin, J. Wahlstrom, E. Law, D.T. Umetsu, and M. Conti PDE4D plays a critical role in the control of airway smooth muscle contraction FASEB J 17 2003 1831 1841 This targeted gene knockout strategy defines the importance of PDE4D in airway smooth muscle contraction.
    • (2003) FASEB J , vol.17 , pp. 1831-1841
    • Mehats, C.1    Jin, S.L.2    Wahlstrom, J.3    Law, E.4    Umetsu, D.T.5    Conti, M.6
  • 22
    • 0034595707 scopus 로고    scopus 로고
    • ERK2 MAP kinase binding, phosphorylation and regulation of PDE4D cAMP specific phosphodiesterases: The involvement of C-terminal docking sites and N-terminal UCR regions
    • S.J. MacKenzie, G.S. Baillie, I. McPhee, G.B. Bolger, and M.D. Houslay ERK2 MAP kinase binding, phosphorylation and regulation of PDE4D cAMP specific phosphodiesterases: the involvement of C-terminal docking sites and N-terminal UCR regions J Biol Chem 275 2000 16609 16617
    • (2000) J Biol Chem , vol.275 , pp. 16609-16617
    • MacKenzie, S.J.1    Baillie, G.S.2    McPhee, I.3    Bolger, G.B.4    Houslay, M.D.5
  • 23
    • 0033558010 scopus 로고    scopus 로고
    • The MAP kinase ERK2 inhibits the cyclic AMP-specific phosphodiesterase HSPDE4D3 by phosphorylating it at Ser579
    • R. Hoffmann, G.S. Baillie, S.J. MacKenzie, S.J. Yarwood, and M.D. Houslay The MAP kinase ERK2 inhibits the cyclic AMP-specific phosphodiesterase HSPDE4D3 by phosphorylating it at Ser579 EMBO J 18 1999 893 903
    • (1999) EMBO J , vol.18 , pp. 893-903
    • Hoffmann, R.1    Baillie, G.S.2    MacKenzie, S.J.3    Yarwood, S.J.4    Houslay, M.D.5
  • 24
    • 0034714376 scopus 로고    scopus 로고
    • Expression of phosphodiesterase 4D (PDE4D) is regulated by both the cyclic AMP-dependent protein kinase and mitogen-activated protein kinase signaling pathways. A potential mechanism allowing for the coordinated regulation of PDE4D activity and expression in cells
    • H. Liu, D. Palmer, S.L. Jimmo, D.G. Tilley, H.A. Dunkerley, S.C. Pang, and D.H. Maurice Expression of phosphodiesterase 4D (PDE4D) is regulated by both the cyclic AMP-dependent protein kinase and mitogen-activated protein kinase signaling pathways. A potential mechanism allowing for the coordinated regulation of PDE4D activity and expression in cells J Biol Chem 275 2000 26615 26624
    • (2000) J Biol Chem , vol.275 , pp. 26615-26624
    • Liu, H.1    Palmer, D.2    Jimmo, S.L.3    Tilley, D.G.4    Dunkerley, H.A.5    Pang, S.C.6    Maurice, D.H.7
  • 25
    • 0034766764 scopus 로고    scopus 로고
    • Phorbol 12-myristate 13-acetate triggers the protein kinase A-mediated phosphorylation and activation of the PDE4D5 cAMP phosphodiesterase in human aortic smooth muscle cells through a route involving extracellular signal regulated kinase (ERK)
    • G. Baillie, S.J. MacKenzie, and M.D. Houslay Phorbol 12-myristate 13-acetate triggers the protein kinase A-mediated phosphorylation and activation of the PDE4D5 cAMP phosphodiesterase in human aortic smooth muscle cells through a route involving extracellular signal regulated kinase (ERK) Mol Pharmacol 60 2001 1100 1111
    • (2001) Mol Pharmacol , vol.60 , pp. 1100-1111
    • Baillie, G.1    MacKenzie, S.J.2    Houslay, M.D.3
  • 26
    • 0034646689 scopus 로고    scopus 로고
    • Short term feedback regulation of cAMP in FRTL-5 thyroid cells. Role of pde4d3 phosphodiesterase activation
    • N. Oki, S.I. Takahashi, H. Hidaka, and M. Conti Short term feedback regulation of cAMP in FRTL-5 thyroid cells. Role of pde4d3 phosphodiesterase activation J Biol Chem 275 2000 10831 10837
    • (2000) J Biol Chem , vol.275 , pp. 10831-10837
    • Oki, N.1    Takahashi, S.I.2    Hidaka, H.3    Conti, M.4
  • 27
    • 0033597139 scopus 로고    scopus 로고
    • Association with the src family tyrosyl kinase lyn triggers a conformational change in the catalytic region of human cAMP-specific phosphodiesterase HSPDE4A4B: Consequences for rolipram inhibition
    • I. McPhee, S.J. Yarwood, E. Huston, G. Scotland, M.B. Beard, A.H. Ross, E.S. Houslay, and M.D. Houslay Association with the src family tyrosyl kinase lyn triggers a conformational change in the catalytic region of human cAMP-specific phosphodiesterase HSPDE4A4B: consequences for rolipram inhibition J Biol Chem 274 1999 11796 11810
    • (1999) J Biol Chem , vol.274 , pp. 11796-11810
    • McPhee, I.1    Yarwood, S.J.2    Huston, E.3    Scotland, G.4    Beard, M.B.5    Ross, A.H.6    Houslay, E.S.7    Houslay, M.D.8
  • 28
    • 0033591233 scopus 로고    scopus 로고
    • The RACK1 signaling scaffold protein selectively interacts with the cAMP-specific phosphodiesterase PDE4D5 isoform
    • S.J. Yarwood, M.R. Steele, G. Scotland, M.D. Houslay, and G.B. Bolger The RACK1 signaling scaffold protein selectively interacts with the cAMP-specific phosphodiesterase PDE4D5 isoform J Biol Chem 274 1999 14909 14917
    • (1999) J Biol Chem , vol.274 , pp. 14909-14917
    • Yarwood, S.J.1    Steele, M.R.2    Scotland, G.3    Houslay, M.D.4    Bolger, G.B.5
  • 29
    • 34248333795 scopus 로고    scopus 로고
    • Delineation of RAID1, the RACK1 interaction domain located within the unique N-terminal region of the cAMP-specific phosphodiesterase, PDE4D5
    • G.B. Bolger, A. McCahill, S.J. Yarwood, M.S. Steele, J. Warwicker, and M.D. Houslay Delineation of RAID1, the RACK1 interaction domain located within the unique N-terminal region of the cAMP-specific phosphodiesterase, PDE4D5 BMC Biochem 3 2002 24
    • (2002) BMC Biochem , vol.3 , pp. 24
    • Bolger, G.B.1    McCahill, A.2    Yarwood, S.J.3    Steele, M.S.4    Warwicker, J.5    Houslay, M.D.6
  • 30
    • 0035815666 scopus 로고    scopus 로고
    • Myomegalin is a novel protein of the golgi/centrosome that interacts with a cyclic nucleotide phosphodiesterase
    • I. Verde, G. Pahlke, M. Salanova, G. Zhang, S. Wang, D. Coletti, J. Onuffer, S.L. Jin, and M. Conti Myomegalin is a novel protein of the golgi/centrosome that interacts with a cyclic nucleotide phosphodiesterase J Biol Chem 276 2001 11189 11198
    • (2001) J Biol Chem , vol.276 , pp. 11189-11198
    • Verde, I.1    Pahlke, G.2    Salanova, M.3    Zhang, G.4    Wang, S.5    Coletti, D.6    Onuffer, J.7    Jin, S.L.8    Conti, M.9
  • 31
    • 0041856176 scopus 로고    scopus 로고
    • Attenuation of the activity of the cAMP-specific phosphodiesterase PDE4A5 by interaction with the immunophilin XAP2
    • G.B. Bolger, A.H. Peden, M.R. Steele, C. MacKenzie, D.G. McEwan, D.A. Wallace, E. Huston, G.S. Baillie, and M.D. Houslay Attenuation of the activity of the cAMP-specific phosphodiesterase PDE4A5 by interaction with the immunophilin XAP2 J Biol Chem 278 2003 33351 33363 The first demonstration that specific protein-protein interactions can affect the ability of PKA to phosphorylate a long PDE4 isoform.
    • (2003) J Biol Chem , vol.278 , pp. 33351-33363
    • Bolger, G.B.1    Peden, A.H.2    Steele, M.R.3    MacKenzie, C.4    McEwan, D.G.5    Wallace, D.A.6    Huston, E.7    Baillie, G.S.8    Houslay, M.D.9
  • 33
    • 0035933817 scopus 로고    scopus 로고
    • Phosphodiesterase 4D and protein kinase a type II constitute a signaling unit in the centrosomal area
    • K.A. Tasken, P. Collas, W.A. Kemmner, O. Witczak, M. Conti, and K. Tasken Phosphodiesterase 4D and protein kinase a type II constitute a signaling unit in the centrosomal area J Biol Chem 276 2001 21999 22002
    • (2001) J Biol Chem , vol.276 , pp. 21999-22002
    • Tasken, K.A.1    Collas, P.2    Kemmner, W.A.3    Witczak, O.4    Conti, M.5    Tasken, K.6
  • 35
    • 3142723295 scopus 로고    scopus 로고
    • Fluorescence resonance energy transfer-based analysis of cAMP dynamics in live neonatal rat cardiac myocytes reveals distinct functions of compartmentalized phosphodiesterases
    • M. Mongillo, T. McSorley, S. Evellin, A. Sood, V. Lissandron, A. Terrin, E. Huston, A. Hannawacker, M.J. Lohse, and T. Pozzan Fluorescence resonance energy transfer-based analysis of cAMP dynamics in live neonatal rat cardiac myocytes reveals distinct functions of compartmentalized phosphodiesterases Circ Res 95 2004 67 75 This study uses a genetically encoded probe to demonstrate the hierarchy of distinct PDE families that underpin cAMP compartmentalisation in cardiac myocytes, in particular the key roles of the PDE3 and PDE4 families.
    • (2004) Circ Res , vol.95 , pp. 67-75
    • Mongillo, M.1    McSorley, T.2    Evellin, S.3    Sood, A.4    Lissandron, V.5    Terrin, A.6    Huston, E.7    Hannawacker, A.8    Lohse, M.J.9    Pozzan, T.10
  • 36
    • 0041353429 scopus 로고    scopus 로고
    • 2-adrenergic stimulation of ICa,L in frog ventricular myocytes
    • 2-adrenergic stimulation of ICa,L in frog ventricular myocytes J Physiol 551 2003 239 252 This study shows that PDEs have a central role in generating compartmentalised cAMP signalling in myocytes.
    • (2003) J Physiol , vol.551 , pp. 239-252
    • Jurevicius, J.1    Skeberdis, V.A.2    Fischmeister, R.3
  • 37
    • 0036499130 scopus 로고    scopus 로고
    • Arresting developments in heptahelical receptor signaling and regulation
    • S.J. Perry, and R.J. Lefkowitz Arresting developments in heptahelical receptor signaling and regulation Trends Cell Biol 12 2002 130 138
    • (2002) Trends Cell Biol , vol.12 , pp. 130-138
    • Perry, S.J.1    Lefkowitz, R.J.2
  • 38
    • 0034787539 scopus 로고    scopus 로고
    • Characterization of arrestin expression and function
    • S.J. Mundell, M.J. Orsini, and J.L. Benovic Characterization of arrestin expression and function Methods Enzymol 343 2002 600 611
    • (2002) Methods Enzymol , vol.343 , pp. 600-611
    • Mundell, S.J.1    Orsini, M.J.2    Benovic, J.L.3
  • 40
    • 1542572127 scopus 로고    scopus 로고
    • The unique amino-terminal region of the PDE4D5 cAMP phosphodiesterase isoform confers preferential interaction with β-arrestins
    • G.B. Bolger, A. McCahill, E. Huston, Y.F. Cheung, T. McSorley, G.S. Baillie, and M.D. Houslay The unique amino-terminal region of the PDE4D5 cAMP phosphodiesterase isoform confers preferential interaction with β-arrestins J Biol Chem 278 2003 49230 49238 The first identification that PDE4D5 is the 'preferred' form to interact with β-arrestin, because of the additional interaction site within its isoform-specific N terminus.
    • (2003) J Biol Chem , vol.278 , pp. 49230-49238
    • Bolger, G.B.1    McCahill, A.2    Huston, E.3    Cheung, Y.F.4    McSorley, T.5    Baillie, G.S.6    Houslay, M.D.7
  • 42
    • 0036839745 scopus 로고    scopus 로고
    • Dancing with different partners: Protein kinase a phosphorylation of seven membrane-spanning receptors regulates their G-protein-coupling specificity
    • R.J. Lefkowitz, K.L. Pierce, and L.M. Luttrell Dancing with different partners: protein kinase a phosphorylation of seven membrane-spanning receptors regulates their G-protein-coupling specificity Mol Pharmacol 62 2002 971 974
    • (2002) Mol Pharmacol , vol.62 , pp. 971-974
    • Lefkowitz, R.J.1    Pierce, K.L.2    Luttrell, L.M.3
  • 43
    • 0037183973 scopus 로고    scopus 로고
    • Cyclic AMP-dependent transcriptional up-regulation of phosphodiesterase 4D5 in human airway smooth muscle cells. Identification and characterization of a novel PDE4D5 promoter
    • I.R. Le Jeune, M. Shepherd, G. Van Heeke, M.D. Houslay, and I.P. Hall Cyclic AMP-dependent transcriptional up-regulation of phosphodiesterase 4D5 in human airway smooth muscle cells. Identification and characterization of a novel PDE4D5 promoter J Biol Chem 277 2002 35980 35989
    • (2002) J Biol Chem , vol.277 , pp. 35980-35989
    • Le Jeune, I.R.1    Shepherd, M.2    Van Heeke, G.3    Houslay, M.D.4    Hall, I.P.5
  • 44
    • 6344233216 scopus 로고    scopus 로고
    • TCR- and CD28-mediated recruitment of phosphodiesterase 4 to lipid rafts potentiates TCR signaling
    • H. Abrahamsen, G. Baillie, J. Ngai, T. Vang, K. Nika, A. Ruppelt, T. Mustelin, M. Zaccolo, M. Houslay, and K. Tasken TCR- and CD28-mediated recruitment of phosphodiesterase 4 to lipid rafts potentiates TCR signaling J Immunol 173 2004 4847 4858 This study is the first to find that ligation of the TCR and CD28 can cause the recruitment of both β-arrestin and PDE4 isoforms to lipid rafts. This gives key, novel insight into a means whereby CD28 serves to augment T-cell activation upon liganding of the TCR by recruiting PDE4, which acts to lower (localised) cAMP levels, thereby attenuating the inhibitory action of AKAP-anchored PKA exerted through the Csk.
    • (2004) J Immunol , vol.173 , pp. 4847-4858
    • Abrahamsen, H.1    Baillie, G.2    Ngai, J.3    Vang, T.4    Nika, K.5    Ruppelt, A.6    Mustelin, T.7    Zaccolo, M.8    Houslay, M.9    Tasken, K.10


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