The SH3 domain of Bruton's tyrosine kinase interacts with Vav, Sam68 and EWS.
Bruton tyrosine kinase (BTK) is a cytoplasmic protein tyrosine kinase which controls crucial steps of differentiation of B lymphocytes. Mutations affecting either the PH, SH3, SH2 or kinase domain of BTK all give rise to X linked agammaglobulinaemia (XLA) in humans. In this study, the authors report that the BTK-SH3 domain binds to a set of proteins expressed in pro-B, pre-B and B cell lines. Three of them were characterized as Vav, Sam68 and EWS. The authors show that a Pro-->Leu substitution in a region of the SH3 domain, which is deleted in an XLA patient, is sufficient to abolish BTK-SH3 binding potential. The authors also report that several of the BTK-SH3 binding proteins, including Sam68, EWS and Vav, are tyrosine phosphorylated in conditions that also promote BTK kinase activity. For EWS and Sam68 this tyrosine phosphorylation was cell cycle dependent.
Guinamard
R
R
Centre d'Immunologie INSERM-CNRS de Marseille-Luminy (CIML), Marseille, France.
Fougereau
M
M
Seckinger
P
P
D048868:Adaptor Proteins, Signal Transducing; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000201:enzymology; D002453:Cell Cycle / Q000276:immunology; D018797:Cell Cycle Proteins; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000276:immunology; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000378:metabolism*; D051567:Proto-Oncogene Proteins c-vav; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000096:biosynthesis / Q000378:metabolism*; D012512:Sarcoma, Ewing / Q000201:enzymology; D014443:Tyrosine / Q000378:metabolism; D018909:src Homology Domains / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C074561:GAP-associated protein p62; D034441:Heterogeneous-Nuclear Ribonucleoproteins; C489559:KHDRBS1 protein, human; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C496618:VAV1 protein, human; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human