Oligomerization of signaling complexes by the multipoint binding of GRB2 to both LAT and SOS1
- 13 August 2006
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Structural & Molecular Biology
- Vol. 13 (9), 798-805
- https://doi.org/10.1038/nsmb1133
Abstract
Receptor oligomerization is vital for activating intracellular signaling, in part by initiating events that recruit effector and adaptor proteins to sites of active signaling. Whether these distal molecules themselves oligomerize is not well appreciated. In this study, we examined the molecular interactions of the adaptor protein GRB2. In T cells, the SH2 domain of GRB2 binds phosphorylated tyrosines on the adaptor protein LAT and the GRB2 SH3 domains associate with the proline-rich regions of SOS1 and CBL. Using biochemical and biophysical techniques in conjunction with confocal microscopy, we observed that the simultaneous association of GRB2, via its SH2 and SH3 domains, with multivalent ligands led to the oligomerization of these ligands, which affected signaling. These data suggest that multipoint binding of distal adaptor proteins mediates the formation of oligomeric signaling clusters vital for intracellular signaling.Keywords
This publication has 38 references indexed in Scilit:
- The p85 regulatory subunit of phosphoinositide 3-kinase down-regulates IRS-1 signaling via the formation of a sequestration complexThe Journal of cell biology, 2005
- Structural Analysis of Autoinhibition in the Ras Activator Son of SevenlessCell, 2004
- Binding Specificity of Multiprotein Signaling Complexes Is Determined by Both Cooperative Interactions and Affinity PreferencesBiochemistry, 2004
- Dynamic changes in the mobility of LAT in aggregated lipid rafts upon T cell activationThe Journal of cell biology, 2003
- T cell receptor ligation induces the formation of dynamically regulated signaling assembliesThe Journal of cell biology, 2002
- Signal Transduction Mediated by the T Cell Antigen Receptor: The Role of Adapter ProteinsAnnual Review of Immunology, 2002
- Solution structure of Grb2 reveals extensive flexibility necessary for target recognitionJournal of Molecular Biology, 2001
- Size-Distribution Analysis of Macromolecules by Sedimentation Velocity Ultracentrifugation and Lamm Equation ModelingBiophysical Journal, 2000
- The Grb2-mSos1 Complex Binds Phosphopeptides with Higher Affinity than Grb2Published by Elsevier BV ,1996
- Crystal Structure of the Mammalian Grb2 AdaptorScience, 1995