Submitted Manuscript: Confidential DAY MONTH YEAR Science Signaling Manuscript Template General Instructions on using this template and submitting a manuscript to Science Signaling: Using this template will help to speed the processing of your paper. Our goal is to be able to identify each section of your manuscript so that we can accurately record the title, authors, abstract, etc. and also be able to enrich it by including reference links and an accurate layout. This template will allow you to prepare your revised manuscript as a Microsoft Word .docx file, which is required for submission. Please use the actual template, which starts on page 2. When you are ready to submit, please delete the text on this cover page. Submit your paper at https://cts.sciencemag.org Additional instructions are available at http://stke.sciencemag.org/about/help/research Specific formatting instructions are provided in the actual template, which follows. Title: Insert Your Title Here of Not More than 135 Characters Including Spaces Authors: F. M. Lastname1*, S. I. Lastname1,2, T. I. Lastname3† [The author list should be one single paragraph (no breaks). Authors should be listed by first name, then middle initial, if any, followed by last name and separated by commas. Use superscript numbers to link affiliations, and symbols *†‡ for author notes. ] One Sentence Summary: This is a single sentence briefly summarizing the paper with not more than 90 characters, including spaces. Affiliations: 1 Affiliations should be preceded by superscript numbers corresponding to the author list, and each affiliation should end with a period. 2 Each affiliation should be a separate paragraph. 3 You can include group authors, but please include a list of the actual authors in the Supplementary Materials. *To whom correspondence should be addressed: include the email addresses of the corresponding author(s). Please use the asterisk (*) symbol for the corresponding author information. †Additional author notes should be indicated with symbols (for example, for current addresses). Abstract: The abstract should be one paragraph of about 150 words and may not exeed250 words. It should have the following structure: An opening sentence that sets the question that you address and is comprehensible to the general reader, background content specific to this study, results, and a concluding sentence. [Main Text:] Introduction This should include an Introduction that provides the background of the study and introduces the signaling events or components under investigation and their biological relevance. It should end with a brief summary of the results and conclusion of the research Results Subhead 1: A phrase or a complete sentence This is followed by a Results section, with brief subheadings. Subheadings must be either all complete sentences or all phrases. Subheadings should not end in a period. Your paper may have as many subheadings as are necessary. Subhead 2: All figures and tables cited in order All sections of the results should refer to a figure or table, preferably a data display element that is part of the main text. All figures and figure panels and tables must be presented in order. For example, the description of panel A of figure 3 cannot come before that of panel B of figure 2. The supplementary figures (for example, fig. S1) and tables (table S1) must also be in presented in order. You may include page breaks if you would like to embed the figures within the text instead of at the end of the paper. Subhead 3: All data presented first in the Results All data should be presented in the Results. No data should be presented for the first time in the Discussion. Data should be appropriately quantified. Subhead 4: Formatting in-text reference callouts References should be cited in parentheses with an italic number (1). Multiple reference citations are separated by commas (2, 3) or if a series, dashes (4-6). References are cited in order by where they first are called out, through the text, then the figure legends and tables or table captions, and then through the supplementary materials. Subhead 5: Handling of equations Equations can be included. Do not use the native Word 2007, 2008, 2010, or 2011 equation editor. This can in produce inaccurate MathML, the online markup language we use, which may result in display errors. Instead, use the legacy equation editor in word (Insert menu; select insert object; select word equation) or use Mathtype (recommended). If you enter equations in simple LaTeX, check that they will convert accurately (Word 2007 and higher can convert simple LaTeX equations). Discussion Finally, include a Discussion section that summarizes your conclusions and elaborates on their implications. Avoid claims of priority (for example, this is the first report), and avoid repeating the conclusions at the end. Summary or model figures or tables may be included in the Discussion, but data figures and tables must be presented in the Results first. Materials and Methods Section 1 In general, the materials and methods for all data presented in the main text must be included in the Materials and Methods. Materials and methods that are used only in data presented in the Supplementary Materials may either be included in the main text or may be listed in the Supplementary Materials in a Methods or Materials and Methods section in the Supplementary Materials. We prefer all materials and methods to be part of the main text for most manuscripts. Section 2 Common or routine methods or procedures do not have to be described in detail unless substantially different from those previously reported or modified from the manufacturer’s instructions. All previously reported methods or materials should be properly cited. Section 3 Statistical analysis must be fully described in the manuscript and appropriate to the data analyzed. Data with a non-normal distribution or multiple comparisons should not be analyzed with t-tests. For guidance on selecting an appropriate statistical test, please consult a statistician or statistics textbook. Statistical analyses can be presented in the Materials and Methods or as part of the figure legend, as appropriate. Supplementary Materials [Present a list of the titles of the Supplementary Materials, in the following order: Supplementary text, supplementary figures, supplementary tables, other supplementary files, such as movies, data, interactive images, or database files. Be sure to submit all Supplementary Materials with the manuscript.] Supplementary Text Fig. S1. Title of the first supplementary figure. Fig. S2. Title of the second supplementary figure. Table S1. Title of the first supplementary table. Data file S1. Title of the first supplementary data file. Movie S1. Title of the first supplementary movie. References and Notes 1. There is only one reference list spanning the text, figure captions, tables, and Supplementary Materials. Do not include a second reference list in the Supplementary Materials section. References only cited in the Supplementary Materials section are not counted toward length guidelines. 2. Each reference should be on a separate line ending in a period. For a style guide, see the “Instructions for preparing Research Articles at the revision stage” PDF on the research help page http://stke.sciencemag.org/about/help/research . 3. Include all author names (no et al.), full titles, and full page ranges. 4. You may use a numbered list in Word. 5. Each reference should have a separate number. 6. Do not mix in references with explanatory notes. Acknowledgments: Thank others for any contributions. Funding: Include all funding sources here, including grant numbers and funding agencies. Author contributions: Here describe the contributions of each author (use initials) to the paper. Competing interests: Include any financial interests of the authors that could be perceived as being a conflict of interest. Here also include any awarded or filed patents pertaining to the results presented in the paper. Data and materials availability: If data are in an archive, include the accession number or a placeholder for it. Also include any materials that must be obtained through an MTA. Acknowledgments follow the references and notes but are not numbered. Figures and Tables [If possible, embed the figures within the Word .docx file, either within results or after the acknowledgements. Each figure’s legend should appear immediately after it on the same page. This will facilitate evaluation of the paper. ] Fig. 1. Short title of the first figure. The figure caption should begin with a title (an overall descriptive statement of the figure). The rest of the legend should explain the figure without providing restating information in the Materials and Methods and without providing interpretation or conclusions. Fig. 2. Short title of the second figure. Legends should be placed immediately after each figure. Indicate figure parts with capital letters (A). If you prefer, you can place both the actual figures and captions logically through the text near where they are cited rather than at the end of the file. Do not put the figures in both places. Fig. 3. Short title of the third figure. N values and what they represent (for example, cells, mice, or experiments) must be stated; for data presented as an average, standard deviation or standard error should also be indicated. Statistical tests can be included if not explained in the Materials and Methods or if they are specific to the data in the figure. N of 1 is not acceptable. Table 1. Short title of the first table. Start table captions with a title (short description of the table). Format tables using the Word Table commands and structures. Do not create tables using spaces or tabs. Footnotes should appear under the last row. Supplementary Materials The first page should include a complete list of the Supplementary Materials, including those that are part of the Supplementary Materials Word file and any additional files that cannot be assembled as part of a Word file. Include the text and files of the Supplementary Materials in a single Word .docx file where possible. Supplementary figures should have legends directly below the figure. The Supplementary Materials may cite references, but they must be listed only in the main references and notes list. For references cited in both the main text and Supplementary Materials, use the reference numbering from the main text reference list. For references cited only in the Supplementary Materials, add these to the main text reference list after the last reference cited in the main text (for example, if there are 25 references cited in the main text and there are 3 additional references cited in the Supplementary Materials, references 1-25 will be the main text citations and references 26-28 will be those only cited in the Supplementary Materials). Items appropriate to include in the Supplementary Materials single Word .docx file include: Additional author notes: For example, a complete list of group authors. Supplementary text Figures S1-S# (with the appropriate legend on the same page as the figure) Tables S1-S# Captions for additional files that cannot be embedded into the Word .docx file, but that are included with the submission. Examples include: Movies S1-S# Audio Files S1-S# External Databases S1-S# Data files S1-S#