Orienteering Strategies For a Signaling Maze

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					                                      MAPPING CELLULAR SIGNALING

           Orienteering Strategies
            For a Signaling Maze
                     his joint Special Issue by Science’s Signal Trans-            The Connections Maps are identified as either “canoni-

                     duction Knowledge Environment (STKE) and                  cal” or “specific.” The canonical maps show the generic
                     Science presents important developments in the            pathway module—a sort of consensus view. This type of
                     sprawling field of signal transduction. (Signal           pathway is useful for understanding the general signaling
                     transduction refers to the processes by which             principles of the pathway and how modules are adapted to
                     cells perceive their environment or internal sta-         distinct functions, but are not intended to represent the sit-
       tus and react to such stimuli with appropriate physiological            uation in a real cell at a particular point in time. The spe-
       responses.) The Viewpoints in this issue of Science provide             cific pathways, on the other hand, depict real molecules
       authoritative syntheses that are accessible to the nonspecial-          and only those relations that are experimentally supported
       ist, explaining what a signaling pathway does and why it does           for a particular species, tissue, and cell type. Thus, com-

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       it. Furthermore, this issue highlights new ways in which Sci-           ponents in the specific pathways can be linked to a defined
       ence’s STKE is working with authors to efficiently convey               entry in existing databases that catalog sequence informa-
       complex information. At Science’s STKE, readers can delve               tion on individual genes or proteins.
       deeper into the topic and take advantage of special electronic              The information in the database and maps is highly re-
       features, particularly the “Connections Map” database in                liable. This quality is derived from the efforts of leading
                                             which the details of the          authorities recruited from many areas of signaling, who
                                             signaling pathway are dy-         frequently update the database. These contributing author-
                                             namically displayed and           ites also provide an evaluation of the quality of the evi-
                                             annotated. (STKE is the           dence for any given relation in the maps. We wanted to
                                             first of a series of Knowl-       bring the diversity, importance, and—as one author says—
                                             edge Environments pub-            the “beauty” of these signaling mechanisms that underlie
                                             lished by AAAS. These             so many aspects of biology to all of the readers of Science.
                                             electronic publications           Therefore, we invited the pathway authorities who author
                                             gather a comprehensive            and curate the Connections Maps to write short Viewpoints
                                             set of resources to en-           that capture the essence of their pathway in this issue of
                                             hance access to informa-          Science. (Both the Viewpoints and the pathways at STKE
                                             tion in a fast-moving field       were critically evaluated by peer review.)
                                             like cell signaling.)                 We take a broad view of signaling at STKE and, there-
                                                 Advances in informa-          fore, have represented many sorts of pathways. Some paths
                                             tion technology are re-           can be deadly, like those emanating from members of the
                                             quired in the biological          tumor-necrosis factor receptor family (Chen and Goeddel,
                                             sciences to cope with the         p. 1634 and Wajant, p. 1635), but only when the balance is
                                             amount and complexity of          tipped away from growth-promoting or survival signals
       information that must be handled in the postgenome era.                 sent from the same receptors. The T and B cell antigen re-
       Thus, Science’s STKE has explored a new way of organizing,              ceptors are at the heart of the body’s defenses, and unrav-
       storing, and communicating the essence of our current un-               eling their signaling mechanisms has revealed much about
       derstanding of signaling mechanisms. The Connections                    immunodeficiencies and autoimmune disorders, as well as
       Maps are an interface to a database of authoritative informa-           the function of the healthy immune system (Singer and Ko-
       tion on signaling molecules and their relations with one an-            retzky, p. 1639, and Gauld et al., p. 1641). Estrogen, a
       other.* The reader accesses information through a Web inter-            steroid hormone, doesn’t bother much with signaling inter-
       face that displays dynamically generated maps of the path-              mediates and makes its way right to the nucleus. But how
       ways (created in real time from the database, so there is no            does it interact with one receptor to produce so many dif-
       lag while an artist works on updating a drawing). Symbols in            ferent effects (McDonnell and Norris, p. 1642)? Many
       the maps represent signaling components or the relations be-            pathways have important roles in cellular transformation,
       tween them, and users can access more information just by               like the Wnt/β-catenin pathway that also has critical roles
       clicking on these symbols.                                              in development (Moon et al., p. 1644), or the JAK-STAT
                                                                               pathway, better known for mediating signals from interfer-
       *Access  to the Connections Map database is free to all registered
                                                                               ons and other cytokines (Aaronson and Horvath, p. 1653).
       users of Science’s STKE; the full-text features within Science’s STKE   The signal from transforming growth factor receptors seem
       require an individual or institutional subscription.                    simple enough—just modify a SMAD protein and send it

1632                                    31 MAY 2002       VOL 296      SCIENCE    www.sciencemag.org

                                                        VIEWPOINTS AND CONNECTIONS MAPS
off to regulate transcription in the nucle-       1 6 3 4 TNF-R1 Signaling: A Beautiful Pathway
us. But nature has found room for plenty                   G. Chen and D. V. Goeddel
of interaction with other pathways and                      * TNF Pathway     http://stke.sciencemag.org/cgi/cm/CMP_7107
other modulation along the way (Attisano          1 6 3 5 The Fas Signaling Pathway: More Than a Paradigm
and Wrana, p. 1646).                                       H. Wajant
    The Connections Maps are not limited                    * Fas Signaling Pathway http://stke.sciencemag.org/cgi/cm/CMP_7966
to the animal kingdom, but include plant                    * Fas Signaling in Cardiomyocytes http://stke.sciencemag.org/cgi/cm/CMP_9993
signaling as well. Unlike vertebrate hor-         1 6 3 6 G Protein Pathways
mone receptors, plant receptors for cy-                    S. Neves, P. T. Ram, R. Iyengar
tokinins are histidine kinases that control                 * Gαi Pathway      http://stke.sciencemag.org/cgi/cm/CMP_7430
many aspects of growth and development                      * Gαs Pathway      http://stke.sciencemag.org/cgi/cm/CMP_6634
(Sheen, p. 1650). The lipid jasmonate is a                  * Gαq Pathway      http://stke.sciencemag.org/cgi/cm/CMP_6680
key regulator in plants impacting processes                 * Gα12 Pathway     http://stke.sciencemag.org/cgi/cm/CMP_8022
                                                            * Gα13 Pathway     http://stke.sciencemag.org/cgi/cm/CMP_8809
like reproduction and stress responses.
Although the biochemical pathway to syn-          1 6 3 9 Control of T Cell Function by Positive and Negative Regulators
                        thesize these bioac-               A. L. Singer and G. A. Koretzky
                        tive lipids is well de-             * T Cell Signal Transduction    http://stke.sciencemag.org/cgi/cm/CMP_7019
                        lineated, many genet-
                                                  1 6 4 1 B Cell Antigen Receptor Signaling: Roles in Cell Development and Disease
                        ic components are
                                                            S. B. Gauld, J. M. Dal Porto, J. C. Cambier

                                                                                                                                                       Downloaded from www.sciencemag.org on April 8, 2011
                        waiting to be discov-               * B Cell Antigen Receptor      http://stke.sciencemag.org/cgi/cm/CMP_6909
                        ered (Liechti and
                        Farmer, p. 1649).         1 6 4 2 Connections and Regulation of the Human Estrogen Receptor
                            Vaudry et al. ex-              D. P. McDonnell and J. D. Norris
                        plore how the same                  * Estrogen Receptor Pathway       http://stke.sciencemag.org/cgi/cm/CMP_7006
                        signal can be used        1 6 4 4 The Promise and Perils of Wnt Signaling Through β-Catenin
                        to promote prolifera-              R. T. Moon, B. Bowerman, M. Boutros, N. Perrimon
                        tion in one instance                * Wnt/β-Catenin Pathway http://stke.sciencemag.org/cgi/cm/CMP_5533
                        and differentiation                 * Drosophila Wnt/Fz Pathways http://stke.sciencemag.org/cgi/cm/CMP_6459
                        in another. The phos-               * C. Elegans T Cell Polarity Pathway http://stke.sciencemag.org/cgi/cm/CMP_10440
                                                            * C. Elegans Gonadogenesis Pathway http://stke.sciencemag.org/cgi/cm/CMP_10698
                        phoinositide 3-kinase               * C. Elegans Endoderm Induction http://stke.sciencemag.org/cgi/cm/CMP_6104
                        pathway uses changes                * C. Elegans QL Neuroblast Migration http://stke.sciencemag.org/cgi/cm/CMP_9763
                        in lipids at the cell               * Xenopus Egg Wnt/β-Catenin Pathway http://stke.sciencemag.org/cgi/cm/CMP_6031
                        membrane to recruit
                        appropriate signaling     1 6 4 6 Signal Transduction by the TGF-β Superfamily
molecules that ultimately control growth,                   L. Attisano and J. L. Wrana
                                                            * TGF-β Pathway     http://stke.sciencemag.org/cgi/cm/CMP_9876
survival, migration, and other responses
(Cantley, p. 1655). G protein pathways are        1 6 4 8 Signaling Pathways for PC12 Cell Differentiation: Making the Right Connections
targets of the majority of therapeutic drugs                D. Vaudry, P. J S. Stork, P. Lazarovici, L. E. Elden
currently available, and Neves et al. (p.                   * Differentiation Pathway in PC12 Cells    http://stke.sciencemag.org/cgi/cm/CMP_8038
1636) highlight several such pathways that
                                                  1 6 4 9 The Jasmonate Pathway
regulate fundamental processes from
                                                           R. Liechti and E. E. Farmer
metabolism to learning and memory. Mar-                     * Jasmonate Biochemical Pathway        http://stke.sciencemag.org/cgi/cm/CMP_7361
tin et al. (p. 1652) take us to “infinity and
beyond,” seeking understanding of how             1 6 5 0 Phosphorelay and Transcription Control in Cytokinin Signal Transduction
signals are generated by integrins, proteins               J. Sheen
                                                            * Cytokinin Signaling Pathway http://stke.sciencemag.org/cgi/cm/CMP_9724
that are literally so important that cells can-             * Arabidopsis Cytokinin Signaling Pathway http://stke.sciencemag.org/cgi/cm/CMP_10021
not live without them.
    Please explore the beauty and complex-        1 6 5 2 Integrin Connections Map: To Infinity and Beyond
ity of these pathways and augment your                      K. H. Martin, J. K. Slack, S. A. Boener, C. C. Martin, J. T. Parsons
reading of Science with the innovative tools                * Integrin Signaling Pathway     http://stke.sciencemag.org/cgi/cm/CMP_6880
available online at Science’s STKE. Think         1 6 5 3 A Road Map for Those Who Don’t Know JAK-STAT
of Science’s STKE as a “GPS” enhance-                      D. A. Aaronson and C. M. Horvath
ment to Science’s Compass. You’ll never                     * JAK-STAT Pathway http://stke.sciencemag.org/cgi/cm/CMP_8301
lose your way.                                              * Interferon γ Pathway http://stke.sciencemag.org/cgi/cm/CMP_9590
     –L. BRYAN RAY AND NANCY R. GOUGH                       * STAT3 Pathway http://stke.sciencemag.org/cgi/cm/CMP_9229
                                                            * Type 1 Interferon (IFNα/β) Pathway http://stke.sciencemag.org/cgi/cm/CMP_8390

                                                  1 6 5 5 The Phosphoinositide 3-Kinase Pathway
                                                           L. C. Cantley
                                                            * Phosphoinositide 3-Kinase Pathway       http://stke.sciencemag.org/cgi/cm/CMP_6557

                                       www.sciencemag.org     SCIENCE       VOL 296        31 MAY 2002                                              1633

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Description: Orienteering is the use of map and compass directions on the map to visit all points marked in the shortest time to reach all points marked the winner. Orienteering usually located in the forest, countryside and city parks were also conducted in the university campus. Determined by the movement originated in Sweden. Started as a military sports events. "Be asked," these two words first used in 1886, meaning: on the map and compass with the help of not being known across the area. Be asking the real game in 1895 in Stockholm and Oslo, Norway at the camp area, marking the directional movement as the birth of a sports event. Hundred years have elapsed since.