Involvement of SLP-65 and Btk in tumor suppression and malignant transformation of pre-B cells.
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.
Hendriks
Rudi W
RW
Department of Immunology, Erasmus MC Rotterdam, P.O. Box 1738, NL-3000 DR Rotterdam, The Netherlands. r.hendriks@erasmusmc.nl
Kersseboom
Rogier
R
D048868:Adaptor Proteins, Signal Transducing; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology*; D006412:Hematopoietic Stem Cells / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; C113939:B cell linker protein; D002352:Carrier Proteins; D010750:Phosphoproteins; D025521:Tumor Suppressor Proteins; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human