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TSH RECEPTOR AUTOREGULATION

TSH 受体自动调节

基本信息

批准号：
10456019
负责人：
TERRY Francis DAVIES
金额：
--
依托单位：
JAMES J PETERS VA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-01-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10456019
关键词：
Active Sites Adipocytes Agonist Antibodies Antigens Autoimmune Binding Biology Bioluminescence Body part CRISPR/Cas technology Cell physiology Cells Characteristics Co-Immunoprecipitations Cytometry Development Disease Energy Transfer Eye Fatty acid glycerol esters Fibroblasts Fluorescence Fluorescence Resonance Energy Transfer Funding GTP-Binding Proteins Graves&apos Disease Growth and Development function Homeostasis Human Hyperthyroidism Immune Immune response Immunohistochemistry Immunologic Receptors Insulin-Like Growth Factor Receptor Knockout Mice Knowledge Learning Life Cycle Stages Ligands Link Mainstreaming Malignant neoplasm of thyroid Mass Spectrum Analysis Membrane Microdomains Messenger RNA Molecular Monitor Muscle Operative Surgical Procedures Osteoblasts Osteoclasts Pathway interactions Patients Phenotype Phosphorylation Physiology Preparation RNA Splicing Receptor Gene Receptor Signaling Role Route Signal Transduction Site Skin Small Interfering RNA Suspensions System TSH receptor antibody Testing Thyroid Diseases Thyroid Gland Thyroid Hormones Thyrotropin Receptor Tissues Transactivation Variant Western Blotting Woman antagonist autoimmune thyroid disease bone bone cell design dimer experience glycosylation immunoreactivity inhibitor men military veteran novel protein activation receptor receptor expression small molecule src-Family Kinases thyroid associated ophthalmopathies trafficking tumor

项目摘要

SUMMARY The thyroidal TSH receptor (TSHR) is the major control point for thyroid hormone synthesis and release as well as thyroid growth and development and is also expressed in a wide variety of non- thyroid tissues including adipocytes, fibroblasts, osteoclasts, osteoblasts and immune cells. The TSHR is a major antigen in autoimmune thyroid disease, especially Graves' disease. However, the mechanisms by which the TSHR modulates non-thyroidal cells is largely unclear and the autoimmune role of extra-thyroidal TSHRs mostly unknown. In this submission, we intend to explore the detailed biology and immune role of selected extra-thyroidal TSHRs aided by our extensive experience with TSHR analysis in thyroid cells. We have 3 specific aims: Specific Aim 1- Explore the molecular characterization, posttranslational processing and receptor routing of TSHRs in extra-thyroidal human cells. Specific Aim 2- Examine the promiscuity of heterologous receptor interactions and study TSHR transactivation. Specific Aim 3- Analyze the immunoreactivity of extra thyroidal TSHRs Although the thyroidal TSHR has been extensively explored, the recognition of extra-thyroidal TSHR expression has revealed a large gap in our knowledge. Information already generated suggests that such sites are active and modulate receptor biology and disease as our studies on bone cells and TSHR-KO mice have illustrated. However, concerns that such TSHRs are immunologically suppressed remain unexplored. Large gaps in our knowledge of the receptor biology of these extra thyroidal tissues exist and our studies will begin to clarify some of these questions.

总结