Discovering Immediate-Early Events in Hedgehog Signal Transduction

发现 Hedgehog 信号转导中的即早期事件

• 批准号: 8493645
• 负责人: Matthew P. Scott
• 金额: $ 19.63万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8493645
• 关键词: Adult; Amino Acids; Animals; Applied Genetics; Basal Cell Nevus Syndrome; Cell Culture Techniques; Cell Differentiation process; Cell Shape; Cells; Cerebellum; Childhood; Cilia; Complex; Congenital Abnormality; Cyclic AMP-Dependent Protein Kinases; Cytoplasmic Granules; Destinations; Development; Drosophila genus; Embryo; Erinaceidae; Event; Genetic; Genetic Transcription; Glycogen Synthase Kinase 3; Goals; Healed; Holoprosencephaly; Human; Human Development; Investigation; Learning; Ligand Binding; Ligands; Link; Malignant Neoplasms; Malignant neoplasm of brain; Maps; Mass Spectrum Analysis; Measures; Medicine; Metabolism; Mitogens; Molecular; Motor; NIH 3T3 Cells; Natural regeneration; Neurons; Organ; Pallister-Hall syndrome; Pathway interactions; Phenotype; Phosphoproteins; Phosphorylation; Pilot Projects; Proliferating; Proteins; Proteome; Proteomics; Regulation; Research; Role; Sampling; Series; Set protein; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Signaling Protein; Stable Isotope Labeling; Staging; Surface; Surface Properties; Surveys; System; Testing; Time; Tissues; Transducers; Vertebrates; Virus Diseases; Work; axon guidance; cancer cell; casein kinase I; cell growth; cell type; fly; healing; hedgehog signal transduction; human SMO protein; innovation; insight; intercellular communication; medulloblastoma; morphogens; notch protein; novel; patched protein; prevent; public health relevance; receptor; regenerative; research study; response; smoothened signaling pathway; tool; trafficking; transcription factor

DESCRIPTION (provided by applicant): The development of most organs and tissues requires signal transduction pathways such as Hedgehog (Hh), TGF1, Notch, and Wnt. Most studies have focused on established components of these pathways, information flow between them, and the relatively slow transcriptional changes they drive. We propose instead a new systematic approach to discovering important rapid responses to developmental signals, using Hh signaling as a test case. Specific Aim 1: We will identify immediate-early responses to an important developmental signal, Hedgehog, applying Stable Isotope Labeling with Amino acids in Cell culture (SILAC) and mass spectrometry to developmental regulation. Specific Aim 2: We will delineate the functions of "re-discovered" components in the Hh immediate-early response and explore novel leads that will provide insight into signal transduction. Summary: Comprehensive assessment of the earliest responses to major developmental signals will reveal new and critical aspects of the signal transduction mechanisms. Our tests using one pathway will set the stage for applying the approach to many others.

描述（申请人提供）：大多数器官和组织的发育都需要信号转导通路，例如Hedgehog（Hh）、TGF1、Notch和Wnt。大多数研究都集中在这些途径的既定组成部分、它们之间的信息流以及它们驱动的相对缓慢的转录变化。相反，我们提出了一种新的系统方法来发现对发育信号的重要快速反应，使用 Hh 信号作为测试用例。具体目标 1：我们将通过细胞培养中氨基酸稳定同位素标记 (SILAC) 和质谱法来确定对重要发育信号 Hedgehog 的早期反应，并应用于发育调节。具体目标 2：我们将描述 Hh 早期反应中“重新发现”成分的功能，并探索新的线索，以深入了解信号转导。摘要：对主要发育信号的最早反应的综合评估将揭示信号转导机制的新的关键方面。我们使用一种途径进行的测试将为将该方法应用于许多其他途径奠定基础。