The Dok-3/Grb2 protein signal module attenuates Lyn kinase-dependent activation of Syk kinase in B cell antigen receptor microclusters
| Autor: | Michael Engelke, Henning Urlaub, Birgit Manno, Hanibal Bohnenberger, Thomas Oellerich, Tim Schnyder, Björn Stork, Marion Lösing, Ingo Goldbeck, Jürgen Wienands, Facundo D. Batista |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
B-cell receptor
Syk Receptors Antigen B-Cell Biology Lymphocyte Activation Biochemistry Mass Spectrometry 03 medical and health sciences 0302 clinical medicine LYN hemic and lymphatic diseases Animals Humans Calcium Signaling Amino Acids Molecular Biology 030304 developmental biology Adaptor Proteins Signal Transducing GRB2 Adaptor Protein 0303 health sciences Microscopy Confocal breakpoint cluster region Cell Biology Cell biology Enzyme Activation src-Family Kinases biology.protein Cancer research Calcium GRB2 Signal transduction biological phenomena cell phenomena and immunity Chickens 030215 immunology Proto-oncogene tyrosine-protein kinase Src Signal Transduction |
| Zdroj: | Journal of Biological Chemistry |
| Popis: | Recruitment of the growth factor receptor-bound protein 2 (Grb2) by the plasma membrane-associated adapter protein downstream of kinase 3 (Dok-3) attenuates signals transduced by the B cell antigen receptor (BCR). Here we describe molecular details of Dok-3/Grb2 signal integration and function, showing that the Lyn-dependent activation of the BCR transducer kinase Syk is attenuated by Dok-3/Grb2 in a site-specific manner. This process is associated with the SH3 domain-dependent translocation of Dok-3/Grb2 complexes into BCR microsignalosomes and augmented phosphorylation of the inhibitory Lyn target SH2 domain-containing inositol 5' phosphatase. Hence, our findings imply that Dok-3/Grb2 modulates the balance between activatory and inhibitory Lyn functions with the aim to adjust BCR signaling efficiency. |
| Databáze: | OpenAIRE |
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