Abstract
Signals from the precursor-B cell receptor (pre-BCR) are essential for selection and clonal expansion of pre-B cells that have performed productive immunoglobulin heavy chain V(D)J recombination. In the mouse, the downstream signaling molecules SLP-65 and Btk cooperate to limit proliferation and induce differentiation of pre-B cells, thereby acting as tumor suppressors to prevent pre-B cell leukemia. In contrast, recent observations in human BCR-ABL1(+) pre-B lymphoblastic leukemia cells demonstrate that Btk is constitutively phosphorylated and activated by the BCR-ABL1 fusion protein. As a result, activated Btk transmits survival signals that are essential for the transforming activity of oncogenic Abl tyrosine kinase.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Adaptor Proteins, Signal Transducing
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Agammaglobulinaemia Tyrosine Kinase
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Animals
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B-Lymphocytes / enzymology
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B-Lymphocytes / metabolism*
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B-Lymphocytes / pathology
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Carrier Proteins / genetics
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Carrier Proteins / physiology*
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Cell Transformation, Neoplastic / metabolism*
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Cell Transformation, Neoplastic / pathology*
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Hematopoietic Stem Cells / enzymology
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Hematopoietic Stem Cells / metabolism*
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Hematopoietic Stem Cells / pathology
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Humans
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Phosphoproteins / genetics
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Phosphoproteins / physiology*
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / physiology*
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / physiology*
Substances
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Adaptor Proteins, Signal Transducing
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B cell linker protein
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Carrier Proteins
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Phosphoproteins
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Tumor Suppressor Proteins
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Protein-Tyrosine Kinases
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Agammaglobulinaemia Tyrosine Kinase
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BTK protein, human