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  • 1
    Publikationsdatum: 2001-09-22
    Beschreibung: The molecular adapter Fyb/Slap regulates signaling downstream of the T cell receptor (TCR), but whether it plays a positive or negative role is controversial. We demonstrate that Fyb/Slap-deficient T cells exhibit defective proliferation and cytokine production in response to TCR stimulation. Fyb/Slap is also required in vivo for T cell-dependent immune responses. Functionally, Fyb/Slap has no apparent role in the activation of known TCR signaling pathways, F-actin polymerization, or TCR clustering. Rather, Fyb/Slap regulates TCR-induced integrin clustering and adhesion. Thus, Fyb/Slap is the first molecular adapter to be identified that couples TCR stimulation to the avidity modulation of integrins governing T cell adhesion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Griffiths, E K -- Krawczyk, C -- Kong, Y Y -- Raab, M -- Hyduk, S J -- Bouchard, D -- Chan, V S -- Kozieradzki, I -- Oliveira-Dos-Santos, A J -- Wakeham, A -- Ohashi, P S -- Cybulsky, M I -- Rudd, C E -- Penninger, J M -- New York, N.Y. -- Science. 2001 Sep 21;293(5538):2260-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Amgen Institute, 620 University Avenue, Toronto, Ontario, Canada M5G 2C1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11567140" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Actins/metabolism ; *Adaptor Proteins, Signal Transducing ; Animals ; Antigens, CD/metabolism ; Antigens, CD3/metabolism ; Antigens, Differentiation, T-Lymphocyte/metabolism ; B-Lymphocytes/immunology ; Carrier Proteins/genetics/*physiology ; Cell Adhesion ; Cell Adhesion Molecules/metabolism ; Chimera ; Gene Targeting ; Humans ; Immunization ; Immunoglobulin G/biosynthesis ; Integrins/*metabolism ; Intercellular Adhesion Molecule-1/metabolism ; Interferon-gamma/biosynthesis ; Interleukin-2/biosynthesis/pharmacology ; Lectins, C-Type ; *Lymphocyte Activation ; Lymphocyte Function-Associated Antigen-1/metabolism ; Mice ; Phosphoproteins/genetics/*physiology ; Receptors, Antigen, T-Cell/immunology/metabolism ; Receptors, Interleukin-2/metabolism ; Recombinant Proteins/metabolism ; Signal Transduction ; T-Lymphocytes/immunology/metabolism/*physiology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    Publikationsdatum: 2000-02-11
    Beschreibung: Phosphoinositide 3-kinases (PI3Ks) regulate fundamental cellular responses such as proliferation, apoptosis, cell motility, and adhesion. Viable gene-targeted mice lacking the p110 catalytic subunit of PI3Kgamma were generated. We show that PI3Kgamma controls thymocyte survival and activation of mature T cells but has no role in the development or function of B cells. PI3Kgamma-deficient neutrophils exhibited severe defects in migration and respiratory burst in response to heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPCR) agonists and chemotactic agents. PI3Kgamma links GPCR stimulation to the formation of phosphatidylinositol 3,4,5-triphosphate and the activation of protein kinase B, ribosomal protein S6 kinase, and extracellular signal-regulated kinases 1 and 2. Thus, PI3Kgamma regulates thymocyte development, T cell activation, neutrophil migration, and the oxidative burst.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sasaki, T -- Irie-Sasaki, J -- Jones, R G -- Oliveira-dos-Santos, A J -- Stanford, W L -- Bolon, B -- Wakeham, A -- Itie, A -- Bouchard, D -- Kozieradzki, I -- Joza, N -- Mak, T W -- Ohashi, P S -- Suzuki, A -- Penninger, J M -- New York, N.Y. -- Science. 2000 Feb 11;287(5455):1040-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Amgen Institute, 620 University Avenue, Toronto M5G 2C1, Ontario, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10669416" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Antigens, CD/analysis ; Apoptosis ; Cell Line ; Chemotactic Factors/pharmacology ; Chemotaxis, Leukocyte/*physiology ; Heterotrimeric GTP-Binding Proteins/metabolism ; Lymph Nodes/cytology ; *Lymphocyte Activation ; Mice ; Mice, Knockout ; Mitogen-Activated Protein Kinases/metabolism ; Neutrophils/*physiology ; Peritonitis/immunology ; Phosphatidylinositol 3-Kinases/*metabolism ; Phosphatidylinositol Phosphates/metabolism ; *Protein-Serine-Threonine Kinases ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-akt ; Respiratory Burst ; Signal Transduction ; Spleen/cytology ; T-Lymphocytes/cytology/*immunology ; Thymus Gland/*cytology/immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
    BibTip Andere fanden auch interessant ...
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