Abstract
In this study, we present the further characterization of a mutant Jurkat T cell line, J.CaM2, that is defective in TCR-mediated signal transduction. Although initial TCR-mediated signaling events such as the inducible tyrosine phosphorylation of the TCR-zeta chain and ZAP-70 are intact in J.CaM2, subsequent events, including increases in intracellular calcium, Ras activation, and IL-2 gene expression are defective. Subsequent analysis of J.CaM2 demonstrated a severe deficiency in pp36/LAT expression, a recently cloned adaptor protein implicated in TCR signaling. Importantly, reexpression of LAT in J.CaM2 restored all aspects of TCR signaling. These results demonstrate a necessary and exclusive role for LAT in T cell activation.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Antigens, CD / biosynthesis
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Antigens, Differentiation, T-Lymphocyte / biosynthesis
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Calcium / metabolism
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Carrier Proteins / physiology*
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DNA-Binding Proteins / physiology
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Enzyme Activation / physiology
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Gene Expression Regulation / physiology
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Humans
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Interleukin-2 / biosynthesis
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Interleukin-2 / genetics
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Isoenzymes / metabolism*
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Jurkat Cells / enzymology
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Jurkat Cells / metabolism
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Lectins, C-Type
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Membrane Proteins*
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Mutation
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NFATC Transcription Factors
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Nuclear Proteins*
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Phospholipase C gamma
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Phosphoproteins / metabolism
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Phosphoproteins / physiology*
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Phosphorylation
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Protein-Tyrosine Kinases / metabolism
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Receptors, Antigen, T-Cell / physiology*
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Signal Transduction / physiology*
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Transcription Factor AP-1 / physiology
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Transcription Factors / physiology
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Type C Phospholipases / metabolism*
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Tyrosine / metabolism
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ZAP-70 Protein-Tyrosine Kinase
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ras Proteins / physiology*
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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CD69 antigen
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Carrier Proteins
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DNA-Binding Proteins
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Interleukin-2
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Isoenzymes
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LAT protein, human
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Lectins, C-Type
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Membrane Proteins
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NFATC Transcription Factors
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Nuclear Proteins
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Phosphoproteins
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Receptors, Antigen, T-Cell
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SLP-76 signal Transducing adaptor proteins
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Transcription Factor AP-1
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Transcription Factors
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Tyrosine
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Protein-Tyrosine Kinases
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ZAP-70 Protein-Tyrosine Kinase
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ZAP70 protein, human
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Calcium-Calmodulin-Dependent Protein Kinases
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Type C Phospholipases
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Phospholipase C gamma
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ras Proteins
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Calcium