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Science 12 November 1999:
Vol. 286. no. 5443, pp. 1358 - 1362
DOI: 10.1126/science.286.5443.1358
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Reports

Cell Survival Promoted by the Ras-MAPK Signaling Pathway by Transcription-Dependent and -Independent Mechanisms

Azad Bonni, * Anne Brunet, Anne E. West, Sandeep Robert Datta, Mari A. Takasu, Michael E. Greenberg dagger

A mechanism by which the Ras-mitogen-activated protein kinase (MAPK) signaling pathway mediates growth factor-dependent cell survival was characterized. The MAPK-activated kinases, the Rsks, catalyzed the phosphorylation of the pro-apoptotic protein BAD at serine 112 both in vitro and in vivo. The Rsk-induced phosphorylation of BAD at serine 112 suppressed BAD-mediated apoptosis in neurons. Rsks also are known to phosphorylate the transcription factor CREB (cAMP response element-binding protein) at serine 133. Activated CREB promoted cell survival, and inhibition of CREB phosphorylation at serine 133 triggered apoptosis. These findings suggest that the MAPK signaling pathway promotes cell survival by a dual mechanism comprising the posttranslational modification and inactivation of a component of the cell death machinery and the increased transcription of pro-survival genes.

Division of Neuroscience, Children's Hospital, and Department of Neurobiology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
*   Present address: Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.

dagger    To whom correspondence should be addressed. E-mail: greenberg{at}hub.tch.harvard.edu

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PKC-{varepsilon}-dependent survival signals in diabetic hearts.
A. Malhotra, R. Begley, B. P. S. Kang, I. Rana, J. Liu, G. Yang, D. Mochly-Rosen, and L. G. Meggs (2005)
Am J Physiol Heart Circ Physiol 289, H1343-H1350
   Abstract »    Full Text »    PDF »
Induction of Competing Apoptotic and Survival Signaling Pathways in the Macrophage by the Ribotoxic Trichothecene Deoxynivalenol.
H.-R. Zhou, Z. Islam, and J. J. Pestka (2005)
Toxicol. Sci. 87, 113-122
   Abstract »    Full Text »    PDF »
Mechanical stimulation prevents osteocyte apoptosis: requirement of integrins, Src kinases, and ERKs.
L. I. Plotkin, I. Mathov, J. I. Aguirre, A. M. Parfitt, S. C. Manolagas, and T. Bellido (2005)
Am J Physiol Cell Physiol 289, C633-C643
   Abstract »    Full Text »    PDF »
Calcium-activated RAF/MEK/ERK Signaling Pathway Mediates p53-dependent Apoptosis and Is Abrogated by {alpha}B-Crystallin through Inhibition of RAS Activation.
D. W.-C. Li, J.-P. Liu, Y.-W. Mao, H. Xiang, J. Wang, W.-Y. Ma, Z. Dong, H. M. Pike, R. E. Brown, and J. C. Reed (2005)
Mol. Biol. Cell 16, 4437-4453
   Abstract »    Full Text »    PDF »
Heparin-Binding Epidermal Growth Factor-Like Growth Factor Inhibits Cytokine-Induced NF-{kappa}B Activation and Nitric Oxide Production via Activation of the Phosphatidylinositol 3-Kinase Pathway.
V. B. Mehta and G. E. Besner (2005)
J. Immunol. 175, 1911-1918
   Abstract »    Full Text »    PDF »
JNK antagonizes Akt-mediated survival signals by phosphorylating 14-3-3.
J. Sunayama, F. Tsuruta, N. Masuyama, and Y. Gotoh (2005)
J. Cell Biol. 170, 295-304
   Abstract »    Full Text »    PDF »
The duration, magnitude and compartmentalization of ERK MAP kinase activity: mechanisms for providing signaling specificity.
M. Ebisuya, K. Kondoh, and E. Nishida (2005)
J. Cell Sci. 118, 2997-3002
   Abstract »    Full Text »    PDF »
BAD Detects Coincidence of G2/M Phase and Growth Factor Deprivation to Regulate Apoptosis.
A. Hashimoto, K. Hirose, and M. Iino (2005)
J. Biol. Chem. 280, 26225-26232
   Abstract »    Full Text »    PDF »
Circulatory Arrest and Low-Flow Cardiopulmonary Bypass Alter CREB Phosphorylation in Piglet Brain.
T. Zaitseva, G. Schears, S. Schultz, J. Creed, D. Antoni, D. F. Wilson, and A. Pastuszko (2005)
Ann. Thorac. Surg. 80, 245-250
   Abstract »    Full Text »    PDF »
p21-activated Kinase 1 (Pak1)-dependent Phosphorylation of Raf-1 Regulates Its Mitochondrial Localization, Phosphorylation of BAD, and Bcl-2 Association.
S. Jin, Y. Zhuo, W. Guo, and J. Field (2005)
J. Biol. Chem. 280, 24698-24705
   Abstract »    Full Text »    PDF »
Growth factor signalling and resistance to selective oestrogen receptor modulators and pure anti-oestrogens: the use of anti-growth factor therapies to treat or delay endocrine resistance in breast cancer.
R I Nicholson, I R Hutcheson, S E Hiscox, J M Knowlden, M Giles, D Barrow, and J M W Gee (2005)
Endocr. Relat. Cancer 12, S29-S36
   Abstract »    Full Text »    PDF »
Laminin-6 assembles into multimolecular fibrillar complexes with perlecan and participates in mechanical-signal transduction via a dystroglycan-dependent, integrin-independent mechanism.
J. C. R. Jones, K. Lane, S. B. Hopkinson, E. Lecuona, R. C. Geiger, D. A. Dean, E. Correa-Meyer, M. Gonzales, K. Campbell, J. I. Sznajder, et al. (2005)
J. Cell Sci. 118, 2557-2566
   Abstract »    Full Text »    PDF »
Odorant-Induced Activation of Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase in the Olfactory Bulb Promotes Survival of Newly Formed Granule Cells.
N. Miwa and D. R. Storm (2005)
J. Neurosci. 25, 5404-5412
   Abstract »    Full Text »    PDF »
Cooperation of Amphiregulin and Insulin-like Growth Factor-1 Inhibits Bax- and Bad-mediated Apoptosis via a Protein Kinase C-dependent Pathway in Non-small Cell Lung Cancer Cells.
A. Hurbin, J.-L. Coll, L. Dubrez-Daloz, B. Mari, P. Auberger, C. Brambilla, and M.-C. Favrot (2005)
J. Biol. Chem. 280, 19757-19767
   Abstract »    Full Text »    PDF »
A Prostacyclin Analog Prevents Radiocontrast Nephropathy via Phosphorylation of Cyclic AMP Response Element Binding Protein.
T. Yano, Y. Itoh, T. Kubota, T. Sendo, T. Koyama, T. Fujita, K. Saeki, A. Yuo, and R. Oishi (2005)
Am. J. Pathol. 166, 1333-1342
   Abstract »    Full Text »    PDF »
Nuclear Ca2+ and the cAMP Response Element-Binding Protein Family Mediate a Late Phase of Activity-Dependent Neuroprotection.
S. Papadia, P. Stevenson, N. R. Hardingham, H. Bading, and G. E. Hardingham (2005)
J. Neurosci. 25, 4279-4287
   Abstract »    Full Text »    PDF »
Functional Characterization of Human RSK4, a New 90-kDa Ribosomal S6 Kinase, Reveals Constitutive Activation in Most Cell Types.
B. A. Dummler, C. Hauge, J. Silber, H. G. Yntema, L. S. Kruse, B. Kofoed, B. A. Hemmings, D. R. Alessi, and M. Frodin (2005)
J. Biol. Chem. 280, 13304-13314
   Abstract »    Full Text »    PDF »
Systematic Evaluation of Anti-apoptotic Growth Factor Signaling in Vascular Smooth Muscle Cells: ONLY PHOSPHATIDYLINOSITOL 3'-KINASE IS IMPORTANT.
M. Vantler, E. Caglayan, W. H. Zimmermann, A. T. Baumer, and S. Rosenkranz (2005)
J. Biol. Chem. 280, 14168-14176
   Abstract »    Full Text »    PDF »
Mechanisms of Estrogen Receptor Signaling: Convergence of Genomic and Nongenomic Actions on Target Genes.
L. Bjornstrom and M. Sjoberg (2005)
Mol. Endocrinol. 19, 833-842
   Abstract »    Full Text »    PDF »
Inhibition of Src-like Kinases Reveals Akt-dependent and -independent Pathways in Insulin-like Growth Factor I-mediated Oligodendrocyte Progenitor Survival.
Q.-L. Cui, W.-H. Zheng, R. Quirion, and G. Almazan (2005)
J. Biol. Chem. 280, 8918-8928
   Abstract »    Full Text »    PDF »


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