Oligomerization of signaling complexes by the multipoint binding of GRB2 to both LAT and SOS1

Jon C D Houtman; Hiroshi Yamaguchi; Mira Barda-Saad; Alex Braiman; Brent Bowden; Ettore Appella; Peter Schuck; Lawrence E Samelson

doi:10.1038/nsmb1133

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Oligomerization of signaling complexes by the multipoint binding of GRB2 to both LAT and SOS1

Journal article

Peer reviewed

Oligomerization of signaling complexes by the multipoint binding of GRB2 to both LAT and SOS1

Jon C D Houtman, Hiroshi Yamaguchi, Mira Barda-Saad, Alex Braiman, Brent Bowden, Ettore Appella, Peter Schuck and Lawrence E Samelson

Nature structural & molecular biology, Vol.13(9), pp.798-805

09/2006

DOI: 10.1038/nsmb1133

PMID: 16906159

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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.

Adaptor Proteins, Signal Transducing - chemistry

Amino Acid Sequence

Receptors, Antigen, T-Cell - metabolism

Signal Transduction

Jurkat Cells

Proline - metabolism

Humans

SOS1 Protein - metabolism

Molecular Sequence Data

GRB2 Adaptor Protein - chemistry

src Homology Domains

Membrane Proteins - chemistry

Models, Biological

Protein Structure, Quaternary

Phosphopeptides - metabolism

Protein Binding

Ligands

Membrane Proteins - metabolism

Adaptor Proteins, Signal Transducing - metabolism

GRB2 Adaptor Protein - metabolism

SOS1 Protein - chemistry

Details

Title: Subtitle: Oligomerization of signaling complexes by the multipoint binding of GRB2 to both LAT and SOS1
Creators: Jon C D Houtman - Laboratory of Cellular and Molecular Biology, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland 20892, USA
Hiroshi Yamaguchi
Mira Barda-Saad
Alex Braiman
Brent Bowden
Ettore Appella
Peter Schuck
Lawrence E Samelson
Resource Type: Journal article
Publication Details: Nature structural & molecular biology, Vol.13(9), pp.798-805
DOI: 10.1038/nsmb1133
PMID: 16906159
ISSN: 1545-9993
eISSN: 1545-9985
Grant note: Intramural NIH HHS
Language: English
Date published: 09/2006
Academic Unit: Microbiology and Immunology; Internal Medicine
Record Identifier: 9984094218202771

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