The Dok-3/Grb2 protein signal module attenuates Lyn kinase-dependent activation 
of Syk kinase in B cell antigen receptor microclusters.

Lösing, M.; Goldbeck, I.; Manno, B.; Oellerich, T.; Schnyder, T.; Bohnenberger, H.; Stork, B.; Urlaub, H.; Batista, F. D.; Wienands, J.; Engelke, M.

doi:10.1074/jbc.M112.406546

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Journal Article

The Dok-3/Grb2 protein signal module attenuates Lyn kinase-dependent activation of Syk kinase in B cell antigen receptor microclusters.

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Urlaub, H.
Research Group of Bioanalytical Mass Spectrometry, MPI for biophysical chemistry, Max Planck Society;

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Citation

Lösing, M., Goldbeck, I., Manno, B., Oellerich, T., Schnyder, T., Bohnenberger, H., et al. (2013). The Dok-3/Grb2 protein signal module attenuates Lyn kinase-dependent activation of Syk kinase in B cell antigen receptor microclusters. Journal of Biological Chemistry, 288(4), 2303-2313. doi:10.1074/jbc.M112.406546.

Cite as: https://hdl.handle.net/11858/00-001M-0000-000E-ECF6-8

Abstract

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.