|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 29, 26581-26586, July 19, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Epac belongs to a new family of proteins that can
directly mediate the action of the intracellular second messenger cAMP
by activating a downstream small GTPase Rap1. The Epac/Rap1
pathway represents a novel cAMP-signaling cascade that is independent of the cAMP-dependent protein kinase (PKA). In this study,
we have used fluorescence microscopy to probe the intracellular
targeting of Epac during different stages of the cell division cycle
and the structural features that are important for Epac localization. Our results suggest Epac, endogenous or expressed as a green
fluorescent protein fusion protein, is mainly localized to the nuclear
membrane and mitochondria during interphase in COS-7 cells. Deletion
mutagenesis analysis reveals that whereas the DEP domain is responsible
for membrane association, the mitochondrial-targeting sequence is located at the N terminus. Although Epac predominantly exhibits perinuclear localization in interphase, the subcellular localization of
Epac is cell cycle-dependent. Epac disassociates from the
nuclear membrane and localizes to the mitotic spindle and centrosomes in metaphase. At the end of the cell cycle, Epac is observed to reassociate with the nuclear envelope and concentrate around the contractile ring. Furthermore, overexpression of Epac in COS-7 cells
leads to an increase in multinuclear cell populations. These results suggest that Epac may play an important role in mitosis.
Cell Cycle-dependent Subcellular
Localization of Exchange Factor Directly Activated by cAMP*
,,
Department of Pharmacology and Toxicology,
Sealy Center for Structural Biology, the § Department of
Pathology, World Health Organization Collaborating Center for Tropical
Diseases, and the ¶ Department of Physiology and Biophysics,
School of Medicine, The University of Texas Medical Branch,
Galveston, Texas 77555
*
This work was supported by American Cancer Society Research
Scholar Grant RSG-01-035-01-TBE and National Institutes of Health Center Grant ES06676.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.:
409-772-9656; Fax: 409-772-9642; E-mail: xcheng@utmb.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  B. Ponsioen, M. Gloerich, L. Ritsma, H. Rehmann, J. L. Bos, and K. Jalink Direct Spatial Control of Epac1 by Cyclic AMP Mol. Cell. Biol., May 15, 2009; 29(10): 2521 - 2531. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. G. Chepurny, C. A. Leech, G. G. Kelley, I. Dzhura, E. Dzhura, X. Li, M. J. Rindler, F. Schwede, H. G. Genieser, and G. G. Holz Enhanced Rap1 Activation and Insulin Secretagogue Properties of an Acetoxymethyl Ester of an Epac-selective Cyclic AMP Analog in Rat INS-1 Cells: STUDIES WITH 8-pCPT-2'-O-Me-cAMP-AM J. Biol. Chem., April 17, 2009; 284(16): 10728 - 10736. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Liu, M. Takahashi, Y. Li, S. Song, T. J. Dillon, U. Shinde, and P. J. S. Stork Ras Is Required for the Cyclic AMP-Dependent Activation of Rap1 via Epac2 Mol. Cell. Biol., December 1, 2008; 28(23): 7109 - 7125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Huston, M. J. Lynch, A. Mohamed, D. M. Collins, E. V. Hill, R. MacLeod, E. Krause, G. S. Baillie, and M. D. Houslay EPAC and PKA allow cAMP dual control over DNA-PK nuclear translocation PNAS, September 2, 2008; 105(35): 12791 - 12796. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Das, M. T. Mazhab-Jafari, S. Chowdhury, S. SilDas, R. Selvaratnam, and G. Melacini Entropy-driven cAMP-dependent Allosteric Control of Inhibitory Interactions in Exchange Proteins Directly Activated by cAMP J. Biol. Chem., July 11, 2008; 283(28): 19691 - 19703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Hochbaum, K. Hong, G. Barila, F. Ribeiro-Neto, and D. L. Altschuler Epac, in Synergy with cAMP-dependent Protein Kinase (PKA), Is Required for cAMP-mediated Mitogenesis J. Biol. Chem., February 22, 2008; 283(8): 4464 - 4468. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Violin, L. M. DiPilato, N. Yildirim, T. C. Elston, J. Zhang, and R. J. Lefkowitz {beta}2-Adrenergic Receptor Signaling and Desensitization Elucidated by Quantitative Modeling of Real Time cAMP Dynamics J. Biol. Chem., February 1, 2008; 283(5): 2949 - 2961. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Chen, X. Shi, R. Padmanabhan, Q. Wang, Z. Wu, S. C. Stevenson, M. Hild, D. Garza, and H. Li Identification of novel modulators of mitochondrial function by a genome-wide RNAi screen in Drosophila melanogaster Genome Res., January 1, 2008; 18(1): 123 - 136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Ji, F. C. Mei, B. H. Johnson, E. B. Thompson, and X. Cheng Protein Kinase A, not Epac, Suppresses Hedgehog Activity and Regulates Glucocorticoid Sensitivity in Acute Lymphoblastic Leukemia Cells J. Biol. Chem., December 28, 2007; 282(52): 37370 - 37377. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Brock, F. Fan, F. C. Mei, S. Li, C. Gessner, V. L. Woods Jr., and X. Cheng Conformational Analysis of Epac Activation Using Amide Hydrogen/Deuterium Exchange Mass Spectrometry J. Biol. Chem., November 2, 2007; 282(44): 32256 - 32263. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Dremier, M. Milenkovic, S. Blancquaert, J. E. Dumont, S. O. Doskeland, C. Maenhaut, and P. P. Roger Cyclic Adenosine 3',5'-Monophosphate (cAMP)-Dependent Protein Kinases, But Not Exchange Proteins Directly Activated by cAMP (Epac), Mediate Thyrotropin/cAMP-Dependent Regulation of Thyroid Cells Endocrinology, October 1, 2007; 148(10): 4612 - 4622. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Wayne, H.-Y. Fan, X. Cheng, and J. S. Richards Follicle-Stimulating Hormone Induces Multiple Signaling Cascades: Evidence that Activation of Rous Sarcoma Oncogene, RAS, and the Epidermal Growth Factor Receptor Are Critical for Granulosa Cell Differentiation Mol. Endocrinol., August 1, 2007; 21(8): 1940 - 1957. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Bach, W. T. Kerr, Y. Wang, E. M. Bauman, P. Kine, E. L. Whiteman, R. S. Morgan, E. K. Williamson, E. M. Ostap, J. K. Burkhardt, et al. PI3K regulates pleckstrin-2 in T-cell cytoskeletal reorganization Blood, February 1, 2007; 109(3): 1147 - 1155. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Das and G. Melacini A Model for Agonism and Antagonism in an Ancient and Ubiquitous cAMP-binding Domain J. Biol. Chem., January 5, 2007; 282(1): 581 - 593. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Kang, O. G. Chepurny, B. Malester, M. J. Rindler, H. Rehmann, J. L. Bos, F. Schwede, W. A. Coetzee, and G. G. Holz cAMP sensor Epac as a determinant of ATP-sensitive potassium channel activity in human pancreatic {beta} cells and rat INS-1 cells J. Physiol., June 15, 2006; 573(3): 595 - 609. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Dwivedi, A. C. Mondal, H. S. Rizavi, G. Faludi, M. Palkovits, A. Sarosi, R. R. Conley, and G. N. Pandey Differential and brain region-specific regulation of rap-1 and epac in depressed suicide victims. Arch Gen Psychiatry, June 1, 2006; 63(6): 639 - 648. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. N. Helms, X.-J. Chen, S. Ramosevac, D. C. Eaton, and L. Jain Dopamine regulation of amiloride-sensitive sodium channels in lung cells Am J Physiol Lung Cell Mol Physiol, April 1, 2006; 290(4): L710 - L722. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Sayner, M. Alexeyev, C. W. Dessauer, and T. Stevens Soluble Adenylyl Cyclase Reveals the Significance of cAMP Compartmentation on Pulmonary Microvascular Endothelial Cell Barrier Circ. Res., March 17, 2006; 98(5): 675 - 681. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Wang, T. J. Dillon, V. Pokala, S. Mishra, K. Labudda, B. Hunter, and P. J. S. Stork Rap1-Mediated Activation of Extracellular Signal-Regulated Kinases by Cyclic AMP Is Dependent on the Mode of Rap1 Activation. Mol. Cell. Biol., March 1, 2006; 26(6): 2130 - 2145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Li, S. Asuri, J. F. Rebhun, A. F. Castro, N. C. Paranavitana, and L. A. Quilliam The RAP1 Guanine Nucleotide Exchange Factor Epac2 Couples Cyclic AMP and Ras Signals at the Plasma Membrane J. Biol. Chem., February 3, 2006; 281(5): 2506 - 2514. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Borland, M. Gupta, M. M. Magiera, C. J. Rundell, S. Fuld, and S. J. Yarwood Microtubule-Associated Protein 1B-Light Chain 1 Enhances Activation of Rap1 by Exchange Protein Activated by Cyclic AMP but Not Intracellular Targeting Mol. Pharmacol., January 1, 2006; 69(1): 374 - 384. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Morel, A. Marcantoni, M. Gastineau, R. Birkedal, F. Rochais, A. Garnier, A.-M. Lompre, G. Vandecasteele, and F. Lezoualc'h cAMP-Binding Protein Epac Induces Cardiomyocyte Hypertrophy Circ. Res., December 9, 2005; 97(12): 1296 - 1304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Kang, O. G Chepurny, M. J Rindler, L. Collis, Z. Chepurny, W.-h. Li, M. Harbeck, M. W Roe, and G. G Holz A cAMP and Ca2+ coincidence detector in support of Ca2+-induced Ca2+ release in mouse pancreatic {beta} cells J. Physiol., July 1, 2005; 566(1): 173 - 188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mendez and M. C. LaPointe PGE2-induced hypertrophy of cardiac myocytes involves EP4 receptor-dependent activation of p42/44 MAPK and EGFR transactivation Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2111 - H2117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gupta and S. J. Yarwood MAP1A Light Chain 2 Interacts with Exchange Protein Activated by Cyclic AMP 1 (EPAC1) to Enhance Rap1 GTPase Activity and Cell Adhesion J. Biol. Chem., March 4, 2005; 280(9): 8109 - 8116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. DiPilato, X. Cheng, and J. Zhang Fluorescent indicators of cAMP and Epac activation reveal differential dynamics of cAMP signaling within discrete subcellular compartments PNAS, November 23, 2004; 101(47): 16513 - 16518. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Farina, M. Hattori, J. Qin, Y. Nakatani, N. Minato, and K. Ozato Bromodomain Protein Brd4 Binds to GTPase-Activating SPA-1, Modulating Its Activity and Subcellular Localization Mol. Cell. Biol., October 15, 2004; 24(20): 9059 - 9069. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Novara, P. Baldelli, D. Cavallari, V. Carabelli, A. Giancippoli, and E. Carbone Exposure to cAMP and {beta}-adrenergic stimulation recruits CaV3 T-type channels in rat chromaffin cells through Epac cAMP-receptor proteins J. Physiol., July 15, 2004; 558(2): 433 - 449. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Bundey and P. A. Insel Discrete Intracellular Signaling Domains of Soluble Adenylyl Cyclase: Camps of cAMP? Sci. Signal., May 4, 2004; 2004(231): pe19 - pe19. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Zippin, J. Farrell, D. Huron, M. Kamenetsky, K. C. Hess, D. A. Fischman, L. R. Levin, and J. Buck Bicarbonate-responsive "soluble" adenylyl cyclase defines a nuclear cAMP microdomain J. Cell Biol., February 16, 2004; 164(4): 527 - 534. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. G. Holz Epac: A New cAMP-Binding Protein in Support of Glucagon-Like Peptide-1 Receptor-Mediated Signal Transduction in the Pancreatic {beta}-Cell Diabetes, January 1, 2004; 53(1): 5 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Martemyanov, P. V. Lishko, N. Calero, G. Keresztes, M. Sokolov, K. J. Strissel, I. B. Leskov, J. A. Hopp, A. V. Kolesnikov, C.-K. Chen, et al. The DEP Domain Determines Subcellular Targeting of the GTPase Activating Protein RGS9 In Vivo J. Neurosci., November 12, 2003; 23(32): 10175 - 10181. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Christensen, F. Selheim, J. de Rooij, S. Dremier, F. Schwede, K. K. Dao, A. Martinez, C. Maenhaut, J. L. Bos, H.-G. Genieser, et al. 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 J. Biol. Chem., September 12, 2003; 278(37): 35394 - 35402. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Misra, L. Varticovski, and I. M. Arias Mechanisms by which cAMP increases bile acid secretion in rat liver and canalicular membrane vesicles Am J Physiol Gastrointest Liver Physiol, July 7, 2003; 285(2): G316 - G324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Rehmann, A. Rueppel, J. L. Bos, and A. Wittinghofer Communication between the Regulatory and the Catalytic Region of the cAMP-responsive Guanine Nucleotide Exchange Factor Epac J. Biol. Chem., June 20, 2003; 278(26): 23508 - 23514. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |