The CBL-related protein CBLB participates in FLT3 and interleukin-7 receptor signal transduction in pro-B cells.
The FLT3 receptor tyrosine kinase and its ligand, FL, play an important role in early hematopoietic development. We have found that CBLB, a recently characterized molecule closely related to the CBL protooncogene product, is phosphorylated on tyrosine(s) following FL treatment of JEA2 human pro-B cells and THP1 monocytic cells. Treatment of JEA2 cells with interleukin (IL)-7 induces CBLB phosphorylation as well. FL and IL-7, respectively, induce and increase association of tyrosine-phosphorylated SHC and the p85 subunit of phosphatidylinositol 3'-kinase with CBLB. In these cells, CBLB constitutively binds the GRB2 adaptor predominantly through its N-terminal SH3 domain, to form a complex that is distinct from the GRB2.CBL and GRB2.SOS1 complexes. Together with the fact that CBLB is consistently found in blast cells from acute leukemias and in peripheral blood mononuclear cells, this suggests that CBLB has a role in tyrosine kinase-regulated signaling pathways in many hematolymphoid cells.
Lavagna-Sévenier
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C
Laboratory of Molecular Oncology, INSERM U119, 13009 Marseille, France.
Marchetto
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S
Birnbaum
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D
Rosnet
O
O
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D015703:Antigens, CD / Q000502:physiology*; D051380:GRB2 Adaptor Protein; D005786:Gene Expression Regulation / Q000235:genetics; D006410:Hematopoiesis / Q000502:physiology; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology; D008565:Membrane Proteins / Q000502:physiology*; D050722:Oncogene Protein v-cbl; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D018123:Receptors, Interleukin / Q000502:physiology*; D020395:Receptors, Interleukin-7; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism*; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction / Q000502:physiology*; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014407:Tumor Cells, Cultured; D051941:fms-Like Tyrosine Kinase 3
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D015703:Antigens, CD; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D015851:Interleukin-7; D008565:Membrane Proteins; D050722:Oncogene Protein v-cbl; D011506:Proteins; D011518:Proto-Oncogene Proteins; D018123:Receptors, Interleukin; D020395:Receptors, Interleukin-7; D015682:Retroviridae Proteins, Oncogenic; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; C084881:flt3 ligand protein; D019000:Phosphotyrosine; D019869:Phosphatidylinositol 3-Kinases; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3