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Science 18 December 1998:
Vol. 282. no. 5397, pp. 2275 - 2279
DOI: 10.1126/science.282.5397.2275
Prev | Table of Contents

Reports

A Family of cAMP-Binding Proteins That Directly Activate Rap1

Hiroaki Kawasaki, Gregory M. Springett, Naoki Mochizuki, Shinichiro Toki, Mie Nakaya, Michiyuki Matsuda, David E. Housman, Ann M. Graybiel *

cAMP (3',5' cyclic adenosine monophosphate) is a second messenger that in eukaryotic cells induces physiological responses ranging from growth, differentiation, and gene expression to secretion and neurotransmission. Most of these effects have been attributed to the binding of cAMP to cAMP-dependent protein kinase A (PKA). Here, a family of cAMP-binding proteins that are differentially distributed in the mammalian brain and body organs and that exhibit both cAMP-binding and guanine nucleotide exchange factor (GEF) domains is reported. These cAMP-regulated GEFs (cAMP-GEFs) bind cAMP and selectively activate the Ras superfamily guanine nucleotide binding protein Rap1A in a cAMP-dependent but PKA-independent manner. Our findings suggest the need to reformulate concepts of cAMP-mediated signaling to include direct coupling to Ras superfamily signaling.

H. Kawasaki, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology (MIT), Cambridge, MA, 02139, USA, and Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. G. M. Springett and D. E. Housman, Center for Cancer Research, Department of Biology, MIT, Cambridge, MA, 02139, USA. N. Mochizuki, M. Nakaya, M. Matsuda, Department of Pathology, Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan. S. Toki and A. M. Graybiel, Department of Brain and Cognitive Sciences, MIT, Cambridge, MA, 02139, USA.
*   To whom correspondence should be addressed at the Department of Brain and Cognitive Sciences, Building E25, Room 618, MIT, Cambridge, MA 02139, USA. E-mail: amg{at}wccf.mit.edu

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   Abstract »    Full Text »    PDF »
Death or survival - progesterone-dependent cell fate decisions in the human endometrial stroma..
J J Brosens and B Gellersen (2006)
J. Mol. Endocrinol. 36, 389-398
   Abstract »    Full Text »    PDF »
Beyond the dogma: novel {beta}2-adrenoceptor signalling in the airways..
M. A. Giembycz and R. Newton (2006)
Eur. Respir. J. 27, 1286-1306
   Abstract »    Full Text »    PDF »
Differential and brain region-specific regulation of rap-1 and epac in depressed suicide victims..
Y. Dwivedi, A. C. Mondal, H. S. Rizavi, G. Faludi, M. Palkovits, A. Sarosi, R. R. Conley, and G. N. Pandey (2006)
Arch Gen Psychiatry 63, 639-648
   Abstract »    Full Text »    PDF »
Involvement of protein kinase A in patterning of the mouse somatosensory cortex..
R. F. Watson, R. M. Abdel-Majid, M. W. Barnett, B. S. Willis, A. Katsnelson, T. H. Gillingwater, G. S. McKnight, P. C. Kind, and P. E. Neumann (2006)
J. Neurosci. 26, 5393-5401
   Abstract »    Full Text »    PDF »
Activating Mutations of the Stimulatory G Protein in Juvenile Ovarian Granulosa Cell Tumors: A New Prognostic Factor?.
N. Kalfa, A. Ecochard, C. Patte, P. Duvillard, F. Audran, C. Pienkowski, E. Thibaud, R. Brauner, C. Lecointre, D. Plantaz, et al. (2006)
J. Clin. Endocrinol. Metab. 91, 1842-1847
   Abstract »    Full Text »    PDF »
Compartmentation of Cyclic Nucleotide Signaling in the Heart: The Role of A-Kinase Anchoring Proteins.
K. L. Dodge-Kafka, L. Langeberg, and J. D. Scott (2006)
Circ. Res. 98, 993-1001
   Abstract »    Full Text »    PDF »
Calcium-induced Acrosomal Exocytosis Requires cAMP Acting through a Protein Kinase A-independent, Epac-mediated Pathway.
M. T. Branham, L. S. Mayorga, and C. N. Tomes (2006)
J. Biol. Chem. 281, 8656-8666
   Abstract »    Full Text »    PDF »
Rap1-Mediated Activation of Extracellular Signal-Regulated Kinases by Cyclic AMP Is Dependent on the Mode of Rap1 Activation..
Z. Wang, T. J. Dillon, V. Pokala, S. Mishra, K. Labudda, B. Hunter, and P. J. S. Stork (2006)
Mol. Cell. Biol. 26, 2130-2145
   Abstract »    Full Text »    PDF »
The RAP1 Guanine Nucleotide Exchange Factor Epac2 Couples Cyclic AMP and Ras Signals at the Plasma Membrane.
Y. Li, S. Asuri, J. F. Rebhun, A. F. Castro, N. C. Paranavitana, and L. A. Quilliam (2006)
J. Biol. Chem. 281, 2506-2514
   Abstract »    Full Text »    PDF »
Regulation of sodium-proton exchanger isoform 3 (NHE3) by PKA and exchange protein directly activated by cAMP (EPAC).
K. J. Honegger, P. Capuano, C. Winter, D. Bacic, G. Stange, C. A. Wagner, J. Biber, H. Murer, and N. Hernando (2006)
PNAS 103, 803-808
   Abstract »    Full Text »    PDF »
Microtubule-Associated Protein 1B-Light Chain 1 Enhances Activation of Rap1 by Exchange Protein Activated by Cyclic AMP but Not Intracellular Targeting.
G. Borland, M. Gupta, M. M. Magiera, C. J. Rundell, S. Fuld, and S. J. Yarwood (2006)
Mol. Pharmacol. 69, 374-384
   Abstract »    Full Text »    PDF »
cAMP-Binding Protein Epac Induces Cardiomyocyte Hypertrophy.
E. Morel, A. Marcantoni, M. Gastineau, R. Birkedal, F. Rochais, A. Garnier, A.-M. Lompre, G. Vandecasteele, and F. Lezoualc'h (2005)
Circ. Res. 97, 1296-1304
   Abstract »    Full Text »    PDF »
Epac Activation Converts cAMP from a Proliferative into a Differentiation Signal in PC12 Cells.
S. Kiermayer, R. M. Biondi, J. Imig, G. Plotz, J. Haupenthal, S. Zeuzem, and A. Piiper (2005)
Mol. Biol. Cell 16, 5639-5648
   Abstract »    Full Text »    PDF »
Coordinate Regulation of Forskolin-induced Cellular Proliferation in Macrophages by Protein Kinase A/cAMP-response Element-binding Protein (CREB) and Epac1-Rap1 Signaling: EFFECTS OF SILENCING CREB GENE EXPRESSION ON Akt ACTIVATION.
U. K. Misra and S. V. Pizzo (2005)
J. Biol. Chem. 280, 38276-38289
   Abstract »    Full Text »    PDF »
Multiple roles of Rap1 in hematopoietic cells: complementary versus antagonistic functions.
P. J. S. Stork and T. J. Dillon (2005)
Blood 106, 2952-2961
   Abstract »    Full Text »    PDF »
Hippocampal Neurons Express a Calcineurin-Activated Adenylyl Cyclase.
G. C.-K. Chan, S. Tonegawa, and D. R. Storm (2005)
J. Neurosci. 25, 9913-9918
   Abstract »    Full Text »    PDF »
PKA-Dependent and PKA-Independent Pathways for cAMP-Regulated Exocytosis.
S. Seino and T. Shibasaki (2005)
Physiol Rev 85, 1303-1342
   Abstract »    Full Text »    PDF »
Enhanced Functional Gap Junction Neoformation by Protein Kinase A-Dependent and Epac-Dependent Signals Downstream of cAMP in Cardiac Myocytes.
S. Somekawa, S. Fukuhara, Y. Nakaoka, H. Fujita, Y. Saito, and N. Mochizuki (2005)
Circ. Res. 97, 655-662
   Abstract »    Full Text »    PDF »
cAMP increases Ca2+-dependent exocytosis through both PKA and Epac2 in mouse melanotrophs from pituitary tissue slices.
S. Sedej, T. Rose, and M. Rupnik (2005)
J. Physiol. 567, 799-813
   Abstract »    Full Text »    PDF »
Calcium-sensing soluble adenylyl cyclase mediates TNF signal transduction in human neutrophils.
H. Han, A. Stessin, J. Roberts, K. Hess, N. Gautam, M. Kamenetsky, O. Lou, E. Hyde, N. Nathan, W. A. Muller, et al. (2005)
J. Exp. Med. 202, 353-361
   Abstract »    Full Text »    PDF »


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