Abstract
SHP-1 is a key tyrosine phosphatase that acts as a negative regulator of signal transduction in lymphocytes, which has been found down-regulated in several T cell lines derived from human T cell malignancies. The standardization of a sensitive ELISA for the quantification of SHP-1 protein in peripheral T and B lymphocytes has enabled us to quantify the SHP-1 content of freshly isolated T cells from patients with Sezary syndrome and in the Sezary T cell line HUT-78. In all cases, a dramatic decrease in the content of this protein, when compared with the content in healthy volunteer controls, was observed. These results were corroborated when the expression of SHP-1 mRNA was analyzed. In order to study whether there was any correlation between SHP-1 protein expression and tyrosine phosphorylated state of JAK3, the state of phosphorylation of JAK3 was studied in the T cell line HUT-78, and found to be highly phosphorylated. These results suggest that SHP-1 might be involved in maintaining the IL-2R/JAK3 signaling pathway under control and point towards a role of SHP-1 in the pathogenesis of the disease.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Enzyme Induction
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Enzyme-Linked Immunosorbent Assay
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Gene Expression Regulation, Neoplastic
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Humans
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Intracellular Signaling Peptides and Proteins
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Janus Kinase 3
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Jurkat Cells / metabolism
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / chemistry
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Neoplasm Proteins / genetics
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Neoplasm Proteins / physiology*
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Neoplastic Stem Cells / metabolism*
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Phosphorylation
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Protein Processing, Post-Translational*
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases / biosynthesis
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Protein Tyrosine Phosphatases / genetics
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Protein Tyrosine Phosphatases / physiology*
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Protein-Tyrosine Kinases / chemistry
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Protein-Tyrosine Kinases / physiology*
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RNA, Messenger / biosynthesis
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RNA, Neoplasm / biosynthesis
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Receptors, Interleukin-2 / physiology
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Reverse Transcriptase Polymerase Chain Reaction
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Sensitivity and Specificity
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Sezary Syndrome / metabolism*
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Sezary Syndrome / pathology
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Signal Transduction*
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Skin Neoplasms / metabolism*
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Skin Neoplasms / pathology
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T-Lymphocytes / metabolism*
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Transcription, Genetic
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Tumor Cells, Cultured
Substances
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Intracellular Signaling Peptides and Proteins
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Neoplasm Proteins
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RNA, Messenger
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RNA, Neoplasm
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Receptors, Interleukin-2
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Protein-Tyrosine Kinases
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JAK3 protein, human
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Janus Kinase 3
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PTPN6 protein, human
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases