The Role of Tyrosine Kinase Emt/itk in T-cell Signaling PDF Download
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Author: Keith Anthony Ching
Publisher:
ISBN:
Category : Cellular signal transduction
Languages : en
Pages : 216
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Book Description
Expressed in Mast and T-cells/IL-2 Inducible Tyrosine Kinase (Emt/Itk) is a protein tyrosine kinase required for T-cell antigen receptor (TCR)-induced activation and development. A physical interaction between Emt/Itk and the TCR has not been previously described and the mechanism through which Emt/Itk mediates its effector functions is poorly understood. Here, I have studied the role of Emt/Itk in T-cell antigen receptor (TCR) signal transduction by tracking its localization in response to stimulation through the TCR. Furthermore, I have investigated the mechanism of Emt/Itk localization and activation via interactions with the adapter protein LAT. I have utilized laser-scanning confocal microscopy to demonstrate that antibody-mediated engagement of the CD3[epislon]; chain induces the co-localization of Emt/Itk with TCR/CD3 at the plasma membrane. Removal of the Emt/Itk Pleckstrin Homology domain ([delta]PH-Emt/Itk) abrogates the association of the kinase with the cell membrane, as well as its activation-induced co-localization with the TCR complex and subsequent tyrosine phosphorylation. The addition of a membrane localization sequence from Lck to [delta]PH-Emt/Itk restores its co-localization with the TCR but not its activation-induced tyrosine phosphorylation. The data suggest that the PH domain of Emt/Itk can be replaced with another membrane-localization signal without affecting the membrane targeting and activation-induced colocalization of the kinase with the TCR. However, the PH domain is indispensable for the activation-induced tyrosine phosphorylation of the kinase. I also found that the Emt/Itk SH2 domain is critical for transphosphorylation and activation of Emt/Itk catalytic activity. I show that the Emt/Itk SH2 domain is essential for Emt/Itk to form TCR/CD3 inducible Emt/Itk-LAT complexes whereas the SH3 domain and catalytic activity are not required. I also demonstrate that Emt/Itk-LAT complexes are biologically important because Jurkat T-cells with deficient LAT expression (JCaM2) fail to increase Emt/Itk tyrosine phosphorylation upon TCR/CD3 stimulation. Furthermore, I confirm the stimulation dependent clustering of Emt/Itk and LAT with the TCR complex using confocal microscopy. The present data indicate that the Ernt/Itk SH2 domain mediates the formation of a complex with LAT at the TCR which is essential for Emt/Itk activation and function.
Author: Keith Anthony Ching
Publisher:
ISBN:
Category : Cellular signal transduction
Languages : en
Pages : 216
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Book Description
Expressed in Mast and T-cells/IL-2 Inducible Tyrosine Kinase (Emt/Itk) is a protein tyrosine kinase required for T-cell antigen receptor (TCR)-induced activation and development. A physical interaction between Emt/Itk and the TCR has not been previously described and the mechanism through which Emt/Itk mediates its effector functions is poorly understood. Here, I have studied the role of Emt/Itk in T-cell antigen receptor (TCR) signal transduction by tracking its localization in response to stimulation through the TCR. Furthermore, I have investigated the mechanism of Emt/Itk localization and activation via interactions with the adapter protein LAT. I have utilized laser-scanning confocal microscopy to demonstrate that antibody-mediated engagement of the CD3[epislon]; chain induces the co-localization of Emt/Itk with TCR/CD3 at the plasma membrane. Removal of the Emt/Itk Pleckstrin Homology domain ([delta]PH-Emt/Itk) abrogates the association of the kinase with the cell membrane, as well as its activation-induced co-localization with the TCR complex and subsequent tyrosine phosphorylation. The addition of a membrane localization sequence from Lck to [delta]PH-Emt/Itk restores its co-localization with the TCR but not its activation-induced tyrosine phosphorylation. The data suggest that the PH domain of Emt/Itk can be replaced with another membrane-localization signal without affecting the membrane targeting and activation-induced colocalization of the kinase with the TCR. However, the PH domain is indispensable for the activation-induced tyrosine phosphorylation of the kinase. I also found that the Emt/Itk SH2 domain is critical for transphosphorylation and activation of Emt/Itk catalytic activity. I show that the Emt/Itk SH2 domain is essential for Emt/Itk to form TCR/CD3 inducible Emt/Itk-LAT complexes whereas the SH3 domain and catalytic activity are not required. I also demonstrate that Emt/Itk-LAT complexes are biologically important because Jurkat T-cells with deficient LAT expression (JCaM2) fail to increase Emt/Itk tyrosine phosphorylation upon TCR/CD3 stimulation. Furthermore, I confirm the stimulation dependent clustering of Emt/Itk and LAT with the TCR complex using confocal microscopy. The present data indicate that the Ernt/Itk SH2 domain mediates the formation of a complex with LAT at the TCR which is essential for Emt/Itk activation and function.
Author: Ralph A. Bradshaw
Publisher: Academic Press
ISBN: 0080920918
Category : Science
Languages : en
Pages : 3188
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Book Description
Handbook of Cell Signaling, Three-Volume Set, 2e, is a comprehensive work covering all aspects of intracellular signal processing, including extra/intracellular membrane receptors, signal transduction, gene expression/translation, and cellular/organotypic signal responses. The second edition is an up-to-date, expanded reference with each section edited by a recognized expert in the field. Tabular and well illustrated, the Handbook will serve as an in-depth reference for this complex and evolving field. Handbook of Cell Signaling, 2/e will appeal to a broad, cross-disciplinary audience interested in the structure, biochemistry, molecular biology and pathology of cellular effectors. - Contains over 350 chapters of comprehensive coverage on cell signaling - Includes discussion on topics from ligand/receptor interactions to organ/organism responses - Provides user-friendly, well-illustrated, reputable content by experts in the field
Author:
Publisher: Elsevier
ISBN: 0080466109
Category : Science
Languages : en
Pages : 600
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Book Description
First published in 1943, Vitamins and Hormones is the longest-running serial published by Academic Press. In the early days of the serial, the subjects of vitamins and hormones were quite distinct. The Editorial Board now reflects expertise in the field of hormone action, vitamin action, X-ray crystal structure, physiology, and enzyme mechanisms. Under the capable and qualified editorial leadership of Dr. Gerald Litwack, Vitamins and Hormones continues to publish cutting-edge reviews of interest to endocrinologists, biochemists, nutritionists, pharmacologists, cell biologists, and molecular biologists. Others interested in the structure and function of biologically active molecules like hormones and vitamins will, as always, turn to this series for comprehensive reviews by leading contributors to this and related disciplines.
Author: A.W. Thomson
Publisher: Springer Science & Business Media
ISBN: 9401007659
Category : Medical
Languages : en
Pages : 516
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Book Description
Therapeutic immunosuppression has very broad applications in clinical medicine, ranging from prevention and treatment of organ and bone marrow transplant rejection, management of various autoimmune disorders (e.g., rheumatoid arthritis), skin disease, and asthma. Whereas traditionally only a small repertoire of immunosuppressive agents was available for clinical use, recent discoveries have significantly increased the number of approved agents, resulting in numerous trials to further evaluate their potential. In addition, products of the biotechnology industry - monoclonal antibodies, cytokines, cytokine antagonists, and other products of genetic engineering that target key molecular pathways in disease pathogenesis - have either already made, or are on the verge of making an important impact on treatment. There is also considerable interest in the potential of cell-based therapies (particularly hematopoietic stem and dendritic cell therapy) of allo- and autoimmunity. Important recent advances in the immunotherapy of allergic diseases are also covered in this book. Gene therapy offers considerable promise for suppressing pathogenic processes in either transplantation or autoimmune disorders. The possibility of combining these important new advances to maximize benefit to the patient, and to minimize possible untoward effects (which are also given extensive coverage in this book), is one of the most exciting challenges of contemporary medicine. This volume is intended both for practising physicians and surgeons and for biomedical scientists at the graduate/postdoctoral levels, and is designed to provide the theory behind these various approaches to immunosuppression, and to provide state-of-the-art reviews of current developments in each area. Each chapter is contributed by one or more experts in the field. There was a need to bring this information together in a single volume, as much of the key recent developments have been dispersed throughout the biomedical literature, largely in specialized journals. Since, as in the past, important developments in immunosuppressive therapy in one branch of medicine (i.e. transplantation) are likely to benefit another (e.g., dermatology, rheumatology, gastroenterology), cross-disciplinary coverage of the mechanistic basis of the various therapeutic strategies in a single volume is likely to convey the potential of advances in therapy in the most coherent manner possible.
Author: Antje Chang
Publisher: Springer Science & Business Media
ISBN: 3540856978
Category : Science
Languages : en
Pages : 583
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Book Description
The Springer Handbook of Enzymes provides concise data on some 5,000 enzymes sufficiently well characterized – and here is the second, updated edition. Their application in analytical, synthetic and biotechnology processes as well as in food industry, and for medicinal treatments is added. Data sheets are arranged in their EC-Number sequence. The new edition reflects considerable progress in enzymology: the total material has more than doubled, and the complete 2nd edition consists of 39 volumes plus Synonym Index. Starting in 2009, all newly classified enzymes are treated in Supplement Volumes.
Author: Dietmar Schomburg
Publisher: Springer Science & Business Media
ISBN: 3540478159
Category : Technology & Engineering
Languages : en
Pages : 643
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Book Description
The Springer Handbook of Enzymes provides concise data on some 5,000 enzymes sufficiently well characterized – and here is the second, updated edition. Their application in analytical, synthetic and biotechnology processes as well as in food industry, and for medicinal treatments is added. Data sheets are arranged in their EC-Number sequence. The new edition reflects considerable progress in enzymology: the total material has more than doubled, and the complete 2nd edition consists of 39 volumes plus Synonym Index. Starting in 2009, all newly classified enzymes are treated in Supplement Volumes.
Author:
Publisher:
ISBN:
Category : Medicine
Languages : en
Pages : 266
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Author:
Publisher:
ISBN:
Category : Medicine
Languages : en
Pages : 1892
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Vols. for 1963- include as pt. 2 of the Jan. issue: Medical subject headings.
Author:
Publisher:
ISBN:
Category : Medicine
Languages : en
Pages : 1496
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Author: Dietlinde Wolf
Publisher: Frontiers Media SA
ISBN: 2889766489
Category : Medical
Languages : en
Pages : 180
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Book Description
