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

J Biol Chem. 2013 Jan 25;288(4):2303-13. doi: 10.1074/jbc.M112.406546. Epub 2012 Dec 5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acids / chemistry
  • Animals
  • Calcium / metabolism
  • Calcium Signaling
  • Chickens
  • Enzyme Activation
  • GRB2 Adaptor Protein / metabolism*
  • Humans
  • Lymphocyte Activation
  • Mass Spectrometry / methods
  • Microscopy, Confocal / methods
  • Receptors, Antigen, B-Cell / metabolism*
  • Signal Transduction
  • src-Family Kinases / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Amino Acids
  • DOK3 protein, human
  • GRB2 Adaptor Protein
  • Receptors, Antigen, B-Cell
  • lyn protein-tyrosine kinase
  • src-Family Kinases
  • Calcium