Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 11 September 1998:
Vol. 281. no. 5383, pp. 1625 - 1626
DOI: 10.1126/science.281.5383.1625
Prev | Table of Contents | Next

Perspectives

SIGNAL TRANSDUCTION:
Routing MAP Kinase Cascades

Elaine A. Elion

Cells need to convey information from signals on their surface to a variety of intracellular targets, including transcription factors, contractile proteins, and enzymes. To do so efficiently, they construct information pathways with enzymes called kinases, using the same enzymes over and over. But what prevents cross talk between pathways? In her Perspective, Elion discusses new results in this issue by Whitmarsh et al. and Schaeffer et al., who identify proteins that act as scaffolds in mouse cells, binding certain kinases to make a pathway for a specific function that is insulated from the rest of the cell.

The author is in the Department of Biological Chemistry, Harvard Medical School, Boston, MA 02115, USA. E-mail: elion{at}bcmp.med.harvard.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Three decades of dating recent sediments by fallout radionuclides: a review.
P.G. Appleby (2008)
The Holocene 18, 83-93
   Abstract »    PDF »
MAP kinase pathways.
M. Qi and E. A. Elion (2005)
J. Cell Sci. 118, 3569-3572
   Full Text »    PDF »
Ras-MAPK Pathways.
A. Chan (2005)
Sci. STKE 2005, tr5
   Abstract »    Full Text »    PDF »
Oxidative Stress Activates FUS1 and RLM1 Transcription in the Yeast Saccharomyces cerevisiae in an Oxidant-dependent Manner.
L. Staleva, A. Hall, and S. J. Orlow (2004)
Mol. Biol. Cell 15, 5574-5582
   Abstract »    Full Text »    PDF »
Phosphorylation Regulates KSR1 Stability, ERK Activation, and Cell Proliferation.
G. L. Razidlo, R. L. Kortum, J. L. Haferbier, and R. E. Lewis (2004)
J. Biol. Chem. 279, 47808-47814
   Abstract »    Full Text »    PDF »
Death-Associated Protein Kinase Phosphorylates ZIP Kinase, Forming a Unique Kinase Hierarchy To Activate Its Cell Death Functions.
G. Shani, L. Marash, D. Gozuacik, S. Bialik, L. Teitelbaum, G. Shohat, and A. Kimchi (2004)
Mol. Cell. Biol. 24, 8611-8626
   Abstract »    Full Text »    PDF »
BRCA1 Interacts with and Is Required for Paclitaxel-Induced Activation of Mitogen-Activated Protein Kinase Kinase Kinase 3.
P. M. Gilmore, N. McCabe, J. E. Quinn, R. D. Kennedy, J. J. Gorski, H. N. Andrews, S. McWilliams, M. Carty, P. B. Mullan, W. P. Duprex, et al. (2004)
Cancer Res. 64, 4148-4154
   Abstract »    Full Text »    PDF »
The Molecular Scaffold KSR1 Regulates the Proliferative and Oncogenic Potential of Cells.
R. L. Kortum and R. E. Lewis (2004)
Mol. Cell. Biol. 24, 4407-4416
   Abstract »    Full Text »    PDF »
The SOS3 Family of Calcium Sensors and SOS2 Family of Protein Kinases in Arabidopsis.
D. Gong, Y. Guo, K. S. Schumaker, and J.-K. Zhu (2004)
Plant Physiology 134, 919-926
   Full Text »    PDF »
Epidermal Growth Factor Receptor Autocrine Signaling in RIE-1 Cells Transformed by the Ras Oncogene Enhances Radiation Resistance.
T. M. Grana, C. I. Sartor, and A. D. Cox (2003)
Cancer Res. 63, 7807-7814
   Abstract »    Full Text »    PDF »
Identification of Residues and Domains of Raf Important for Function in Vivo and in Vitro.
A. Harding, V. Hsu, K. Kornfeld, and J. F. Hancock (2003)
J. Biol. Chem. 278, 45519-45527
   Abstract »    Full Text »    PDF »
Recruitment of JNK to JIP1 and JNK-dependent JIP1 Phosphorylation Regulates JNK Module Dynamics and Activation.
D. Nihalani, H. N. Wong, and L. B. Holzman (2003)
J. Biol. Chem. 278, 28694-28702
   Abstract »    Full Text »    PDF »
Mutational Analysis of Stress-responsive Peanut Dual Specificity Protein Kinase. IDENTIFICATION OF TYROSINE RESIDUES INVOLVED IN REGULATION OF PROTEIN KINASE ACTIVITY.
P. Rudrabhatla and R. Rajasekharan (2003)
J. Biol. Chem. 278, 17328-17335
   Abstract »    Full Text »    PDF »
Fibroblast Growth Factor Homologous Factors and the Islet Brain-2 Scaffold Protein Regulate Activation of a Stress-activated Protein Kinase.
J. Schoorlemmer and M. Goldfarb (2002)
J. Biol. Chem. 277, 49111-49119
   Abstract »    Full Text »    PDF »
Activation of Mitogen-activated Protein Kinase Pathway by the Antiandrogen Hydroxyflutamide in Androgen Receptor-negative Prostate Cancer Cells.
Y.-F. Lee, W.-J. Lin, J. Huang, E. M. Messing, F. L. Chan, G. Wilding, and C. Chang (2002)
Cancer Res. 62, 6039-6044
   Abstract »    Full Text »    PDF »
JLP: A scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors.
C. M. Lee, D. Onesime, C. D. Reddy, N. Dhanasekaran, and E. P. Reddy (2002)
PNAS 99, 14189-14194
   Abstract »    Full Text »    PDF »
Biochemical Characterization of the Arabidopsis Protein Kinase SOS2 That Functions in Salt Tolerance.
D. Gong, Y. Guo, A. T. Jagendorf, and J.-K. Zhu (2002)
Plant Physiology 130, 256-264
   Abstract »    Full Text »    PDF »
Cross signaling, cell specificity, and physiology.
J. E. Dumont, S. Dremier, I. Pirson, and C. Maenhaut (2002)
Am J Physiol Cell Physiol 283, C2-C28
   Abstract »    Full Text »    PDF »
Scaffold Role of a Mitogen-activated Protein Kinase Phosphatase, SKRP1, for the JNK Signaling Pathway.
T. Zama, R. Aoki, T. Kamimoto, K. Inoue, Y. Ikeda, and M. Hagiwara (2002)
J. Biol. Chem. 277, 23919-23926
   Abstract »    Full Text »    PDF »
Kinase Suppressor of Ras (KSR) Is a Scaffold Which Facilitates Mitogen-Activated Protein Kinase Activation In Vivo.
A. Nguyen, W. R. Burack, J. L. Stock, R. Kortum, O. V. Chaika, M. Afkarian, W. J. Muller, K. M. Murphy, D. K. Morrison, R. E. Lewis, et al. (2002)
Mol. Cell. Biol. 22, 3035-3045
   Abstract »    Full Text »    PDF »
Kap121p-Mediated Nuclear Import Is Required for Mating and Cellular Differentiation in Yeast.
D. M. Leslie, B. Grill, M. P. Rout, R. W. Wozniak, and J. D. Aitchison (2002)
Mol. Cell. Biol. 22, 2544-2555
   Abstract »    Full Text »    PDF »
The Ste5p scaffold.
E. A. Elion (2002)
J. Cell Sci. 114, 3967-3978
   Abstract »    Full Text »    PDF »
Inhibitory actions of ceramide upon PKC-{epsilon}/ERK interactions.
N. A. Bourbon, J. Yun, D. Berkey, Y. Wang, and M. Kester (2001)
Am J Physiol Cell Physiol 280, C1403-C1411
   Abstract »    Full Text »    PDF »
The Ras Radiation Resistance Pathway.
A. K. Gupta, V. J. Bakanauskas, G. J. Cerniglia, Y. Cheng, E. J. Bernhard, R. J. Muschel, and W. G. McKenna (2001)
Cancer Res. 61, 4278-4282
   Abstract »    Full Text »
Mutations in the YRB1 Gene Encoding Yeast Ran-Binding-Protein-1 That Impair Nucleocytoplasmic Transport and Suppress Yeast Mating Defects.
M. Künzler, J. Trueheart, C. Sette, E. Hurt, and J. Thorner (2001)
Genetics 157, 1089-1105
   Abstract »    Full Text »
A Novel 14-Kilodalton Protein Interacts with the Mitogen-Activated Protein Kinase Scaffold Mp1 on a Late Endosomal/Lysosomal Compartment.
W. Wunderlich, I. Fialka, D. Teis, A. Alpi, A. Pfeifer, R. G. Parton, F. Lottspeich, and L. A. Huber (2001)
J. Cell Biol. 152, 765-776
   Abstract »    Full Text »    PDF »
A Mutation in the Arabidopsis HYL1 Gene Encoding a dsRNA Binding Protein Affects Responses to Abscisic Acid, Auxin, and Cytokinin.
C. Lu and N. Fedoroff (2000)
PLANT CELL 12, 2351-2366
   Abstract »    Full Text »
Targeting the Ras signaling pathway: a rational, mechanism-based treatment for hematologic malignancies?.
C. W. M. Reuter, M. A. Morgan, and L. Bergmann (2000)
Blood 96, 1655-1669
   Abstract »    Full Text »    PDF »
Mechanism of ATP-Induced [Ca2+]i Mobilization in Rat Basilar Smooth Muscle Cells Editorial Comment.
K. Aoki, A. Y. Zubkov, A. D. Parent, J. H. Zhang, and R. L. Macdonald (2000)
Stroke 31, 1377-1385
   Abstract »    Full Text »    PDF »
Scaffold proteins may biphasically affect the levels of mitogen-activated protein kinase signaling and reduce its threshold properties.
A. Levchenko, J. Bruck, and P. W. Sternberg (2000)
PNAS 97, 5818-5823
   Abstract »    Full Text »    PDF »
Mechanism of Suppression of the Raf/MEK/Extracellular Signal-Regulated Kinase Pathway by the Raf Kinase Inhibitor Protein.
K. Yeung, P. Janosch, B. McFerran, D. W. Rose, H. Mischak, J. M. Sedivy, and W. Kolch (2000)
Mol. Cell. Biol. 20, 3079-3085
   Abstract »    Full Text »    PDF »
Protein-protein interactions define specificity in signal transduction.
T. Pawson and P. Nash (2000)
Genes & Dev. 14, 1027-1047
   Full Text »
Synergistic Interaction of MEK Kinase 2, c-Jun N-Terminal Kinase (JNK) Kinase 2, and JNK1 Results in Efficient and Specific JNK1 Activation.
J. Cheng, J. Yang, Y. Xia, M. Karin, and B. Su (2000)
Mol. Cell. Biol. 20, 2334-2342
   Abstract »    Full Text »    PDF »
Identification of Structural and Functional Domains in Mixed Lineage Kinase Dual Leucine Zipper-bearing Kinase Required for Complex Formation and Stress-activated Protein Kinase Activation.
D. Nihalani, S. Merritt, and L. B. Holzman (2000)
J. Biol. Chem. 275, 7273-7279
   Abstract »    Full Text »    PDF »
Multiple Mitogen-Activated Protein Kinase Signaling Pathways Connect the Cot Oncoprotein to the c-jun Promoter and to Cellular Transformation.
M. Chiariello, M. J. Marinissen, and J. S. Gutkind (2000)
Mol. Cell. Biol. 20, 1747-1758
   Abstract »    Full Text »    PDF »
Interaction of a Mitogen-Activated Protein Kinase Signaling Module with the Neuronal Protein JIP3.
N. Kelkar, S. Gupta, M. Dickens, and R. J. Davis (2000)
Mol. Cell. Biol. 20, 1030-1043
   Abstract »    Full Text »    PDF »
Dimer Formation by Ternary Complex Factor ELK-1.
V. Drewett, S. Muller, J. Goodall, and P. E. Shaw (2000)
J. Biol. Chem. 275, 1757-1762
   Abstract »    Full Text »    PDF »
Sterol regulatory element binding proteins (SREBP)-1a and SREBP-2 are linked to the MAP-kinase cascade.
J. Kotzka, D. Müller-Wieland, G. Roth, L. Kremer, M. Munck, S. Schürmann, B. Knebel, and W. Krone (2000)
J. Lipid Res. 41, 99-108
   Abstract »    Full Text »
RIP2 Is a Raf1-activated Mitogen-activated Protein Kinase Kinase.
T. A. Navas, D. T. Baldwin, and T. A. Stewart (1999)
J. Biol. Chem. 274, 33684-33690
   Abstract »    Full Text »    PDF »
Protein Kinase A Anchoring to the Myometrial Plasma Membrane Is Required for Cyclic Adenosine 3',5'-Monophosphate Regulation of Phosphatidylinositide Turnover.
K. L. Dodge, D. W. Carr, and B. M. Sanborn (1999)
Endocrinology 140, 5165-5170
   Abstract »    Full Text »
Distinct Mechanisms Target Stress and Extracellular Signal-Activated Kinase 1 and Jun N-Terminal Kinase During Infection of Macrophages with Salmonella.
K. J. Procyk, M. R. Rippo, R. Testi, F. Hoffmann, P. J. Parker, and M. Baccarini (1999)
J. Immunol. 163, 4924-4930
   Abstract »    Full Text »    PDF »
Arabidopsis NPH3: A NPH1 Photoreceptor-Interacting Protein Essential for Phototropism.
A. Motchoulski and E. Liscum (1999)
Science 286, 961-964
   Abstract »    Full Text »
poc1: An Arabidopsis mutant perturbed in phytochrome signaling because of a T DNA insertion in the promoter of PIF3, a gene encoding a phytochrome-interacting bHLH protein.
K. J. Halliday, M. Hudson, M. Ni, M. Qin, and P. H. Quail (1999)
PNAS 96, 5832-5837
   Abstract »    Full Text »    PDF »
Effects of the NIK aly Mutation on NF-kappa B Activation by the Epstein-Barr Virus Latent Infection Membrane Protein, Lymphotoxin beta Receptor, and CD40.
M. A. Luftig, E. Cahir-McFarland, G. Mosialos, and E. Kieff (2001)
J. Biol. Chem. 276, 14602-14606
   Abstract »    Full Text »    PDF »
Activation of Extracellular-regulated Kinase Pathways in Ovarian Granulosa Cells by the Novel Growth Factor Type 1 Follicle-stimulating Hormone Receptor. ROLE IN HORMONE SIGNALING AND CELL PROLIFERATION.
P. S. Babu, H. Krishnamurthy, P. J. Chedrese, and M. R. Sairam (2000)
J. Biol. Chem. 275, 27615-27626
   Abstract »    Full Text »    PDF »
The Reelin Receptor ApoER2 Recruits JNK-interacting Proteins-1 and -2.
W. Stockinger, C. Brandes, D. Fasching, M. Hermann, M. Gotthardt, J. Herz, W. J. Schneider, and J. Nimpf (2000)
J. Biol. Chem. 275, 25625-25632
   Abstract »    Full Text »    PDF »
MEKK2 Is Required for T-cell Receptor Signals in JNK Activation and Interleukin-2 Gene Expression.
B. Su, J. Cheng, J. Yang, and Z. Guo (2001)
J. Biol. Chem. 276, 14784-14790
   Abstract »    Full Text »    PDF »
A Conserved Docking Site in MEKs Mediates High-affinity Binding to MAP Kinases and Cooperates with a Scaffold Protein to Enhance Signal Transmission.
A. J. Bardwell, L. J. Flatauer, K. Matsukuma, J. Thorner, and L. Bardwell (2001)
J. Biol. Chem. 276, 10374-10386
   Abstract »    Full Text »    PDF »
Regulation of Adipogenesis by a Transcriptional Repressor That Modulates MAPK Activation.
S.-W. Kim, A. M. Muise, P. J. Lyons, and H.-S. Ro (2001)
J. Biol. Chem. 276, 10199-10206
   Abstract »    Full Text »    PDF »
Interaction of the Calcium-sensing Receptor and Filamin, a Potential Scaffolding Protein.
H. Awata, C. Huang, M. E. Handlogten, and R. T. Miller (2001)
J. Biol. Chem. 276, 34871-34879
   Abstract »    Full Text »    PDF »
Regulation of Snf1 Kinase. ACTIVATION REQUIRES PHOSPHORYLATION OF THREONINE 210 BY AN UPSTREAM KINASE AS WELL AS A DISTINCT STEP MEDIATED BY THE Snf4 SUBUNIT.
R. R. McCartney and M. C. Schmidt (2001)
J. Biol. Chem. 276, 36460-36466
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)