Publication Date:
2002-06-18
Description:
Mice homozygous for a single tyrosine mutation in LAT (linker for activation of T cells) exhibited an early block in T cell maturation but later developed a polyclonal lymphoproliferative disorder and signs of autoimmune disease. T cell antigen receptor (TCR)-induced activation of phospholipase C-gamma1 (PLC-gamma1) and of nuclear factor of activated T cells, calcium influx, interleukin-2 production, and cell death were reduced or abrogated in T cells from LAT mutant mice. In contrast, TCR-induced Erk activation was intact. These results identify a critical role for integrated PLC-gamma1 and Ras-Erk signaling through LAT in T cell development and homeostasis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sommers, Connie L -- Park, Cheung-Seog -- Lee, Jan -- Feng, Chiguang -- Fuller, Claudette L -- Grinberg, Alexander -- Hildebrand, Jay A -- Lacana, Emanuela -- Menon, Rashmi K -- Shores, Elizabeth W -- Samelson, Lawrence E -- Love, Paul E -- New York, N.Y. -- Science. 2002 Jun 14;296(5575):2040-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12065840" target="_blank"〉PubMed〈/a〉
Keywords:
*Adaptor Proteins, Signal Transducing
;
Animals
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Antibodies, Antinuclear/blood
;
Antigens, CD5/analysis
;
Autoimmune Diseases/immunology
;
CD4-Positive T-Lymphocytes/immunology/physiology
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Calcium/metabolism
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Calcium Signaling
;
Carrier Proteins/*genetics/*physiology
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Cell Division
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Interleukin-2/biosynthesis
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Isoenzymes/*metabolism
;
Lymphocyte Activation
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Lymphoproliferative Disorders/*etiology/immunology/pathology
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MAP Kinase Signaling System
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*Membrane Proteins
;
Mice
;
Mice, Inbred C57BL
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Mitogen-Activated Protein Kinases/metabolism
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Phenotype
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Phospholipase C gamma
;
Phosphoproteins/*genetics/*physiology
;
Phosphorylation
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*Point Mutation
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Receptors, Antigen, T-Cell/immunology/metabolism
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Signal Transduction
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T-Lymphocyte Subsets/immunology/physiology
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T-Lymphocytes/*immunology/physiology
;
Thymus Gland/cytology/immunology/pathology
;
Transcription Factors/metabolism
;
Type C Phospholipases/*metabolism
;
ras Proteins/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
