The DOI matches its Crossref record.
A High-Affinity Arg-X-X-Lys SH3 Binding Motif Confers Specificity for the Interaction between Gads and SLP-76 in T Cell Signaling
Abstract
A critical event in T cell receptor (TCR)-mediated signaling is the recruitment of hematopoietic-specific adaptor proteins that collect and transmit signals downstream of the TCR. Gads, a member of the Grb2 family of SH2 and SH3 domain-containing adaptors, mediates the formation of a complex between LAT and SLP-76 that is essential for signal propagation from the TCR. Here we examine the binding specificity of the Gads and Grb2 SH3 domains using peptide arrays and find that a nonproline-based R-X-X-K motif found in SLP-76 binds to the Gads carboxy-terminal SH3 domain with high affinity (K(D) = 240 +/- 45 nM). The Grb2 C-terminal SH3 domain also binds this motif, but with a 40-fold lower affinity than Gads. Single point mutations in either the relevant R (237) or K (240) completely abrogated SLP-76 association with Gads in vivo and impaired SLP-76 function. A chimeric Grb2 protein, possessing the C-terminal SH3 domain of Gads, was able to partially substitute for Gads in signaling downstream of the T cell receptor. These results provide a molecular explanation for the specific role of Gads in T cell receptor signaling, and identify a discrete subclass of SH3 domains whose binding is dependent on a core R-X-X-K motif.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Mammalian STAM1/2 proteins interact in vitro with USP8 and AMSH.
“the mammalian STAM1/2 proteins have been shown to interact in vitro with two DUBs: USP8 and the associated molecule with the SH3 domain of STAM (AMSH) (19 -22).”
From Regulation of Epidermal Growth Factor Receptor Ubiquitination and Trafficking by the USP8·STAM Complex (2010) · cites this paper as [19]
Two consensus RXXK motifs had previously been identified in USP8 and shown to interact with the STAM2 SH3 domain.
“Two consensus RXXK motifs had previously been identified in USP8 and shown to interact with the STAM2 SH3 domain (19 -21).”
From Regulation of Epidermal Growth Factor Receptor Ubiquitination and Trafficking by the USP8·STAM Complex (2010) · cites this paper as [19]
A subfamily of SH3 domains binds atypical peptide ligands centered around a consensus RXXK peptide motif.
“We and others have previously reported a subfamily of SH3 domains that bind to atypical peptide ligands centered around a consensus RXXK peptide motif (19 -21, 43-46).”
From Regulation of Epidermal Growth Factor Receptor Ubiquitination and Trafficking by the USP8·STAM Complex (2010) · cites this paper as [19]
We and others have previously reported two motifs in USP8 that interact with atypical SH3 domains of proteins belonging to the Grb2 and STAM adaptor families.
“We and others have previously reported two motifs in USP8 that interact with atypical SH3 domains of proteins belonging to the Grb2 and STAM adaptor families (19,45,51).”
From Regulation of Epidermal Growth Factor Receptor Ubiquitination and Trafficking by the USP8·STAM Complex (2010) · cites this paper as [19]
Each of the three RXXK motifs of USP8 exhibits lower affinities for the RXXK subclass of SH3 domains than previously measured interactions with single RXXK motifs in Slp76, Blnk, Gab1, or Gab2.
“Individually, each of the three RXXK motifs of USP8 was found to exhibit lower affinities for the RXXK subclass of SH3 domains than any of the previously measured interactions with single RXXK motifs in Slp76, Blnk, Gab1, or Gab2 (19).”
From Regulation of Epidermal Growth Factor Receptor Ubiquitination and Trafficking by the USP8·STAM Complex (2010) · cites this paper as [19]
Citations
Cites
No references could be resolved yet.
Research works printed but not linked: 19
- Rudd, 1999, Adaptors and molecular scaffolds in immune cell signaling, Cell, 96, 5, 10.1016/S0092-8674(00)80953-8 · DOI
- Myung, 2000, Adapter proteins in lymphocyte antigen-receptor signaling, Curr. Opin. Immunol., 12, 256, 10.1016/S0952-7915(00)00085-6 · DOI
- Pawson, 2000, Protein-protein interactions define specificity in signal transduction, Genes Dev., 14, 1027, 10.1101/gad.14.9.1027 · DOI
- Liu, 1999, The hematopoietic-specific adaptor protein gads functions in T-cell signaling via interactions with the SLP-76 and LAT adaptors, Curr. Biol., 9, 67, 10.1016/S0960-9822(99)80017-7 · DOI
- Law, 1999, GrpL, a Grb2-related adaptor protein, interacts with SLP-76 to regulate nuclear factor of activated T cell activation, J. Exp. Med., 189, 1243, 10.1084/jem.189.8.1243 · DOI
- Asada, 1999, Grf40, a novel grb2 family member, is involved in T cell signaling through interaction with SLP-76 and LAT, J. Exp. Med., 189, 1383, 10.1084/jem.189.9.1383 · DOI
- Yoder, 2001, Requirement for the SLP-76 adaptor GADS in T cell development, Science, 291, 1987, 10.1126/science.1057176 · DOI
- Motto, 1996, Implication of the GRB2-associated phosphoprotein SLP-76 in T cell receptor-mediated interleukin 2 production, J. Exp. Med., 183, 1937, 10.1084/jem.183.4.1937 · DOI
- Frank, 1992, Spot-synthesis, Tetrahedron, 48, 9217, 10.1016/S0040-4020(01)85612-X · DOI
- Lock, 2000, Identification of an atypical Grb2 carboxyl-terminal SH3 domain binding site in Gab docking proteins reveals Grb2-dependent and -independent recruitment of Gab1 to receptor tyrosine kinases, J. Biol. Chem., 275, 31536, 10.1074/jbc.M003597200 · DOI · Paper page
- Lewitzky, 2001, The C-terminal SH3 domain of the adapter protein Grb2 binds with high affinity to sequences in Gab1 and SLP-76 which lack the SH3-typical P-x-x-P core motif, Oncogene, 20, 1052, 10.1038/sj.onc.1204202 · DOI · Paper page
- Qiu, 1998, Molecular cloning and expression of human grap-2, a novel leukocyte-specific SH2- and SH3-containing adaptor-like protein that binds to gab-1, Biochem. Biophys. Res. Commun., 253, 443, 10.1006/bbrc.1998.9795 · DOI
- Frank, 1996, SPOT synthesis. Epitope analysis with arrays of synthetic peptides prepared on cellulose membranes, Methods Mol. Biol., 66, 149
- Myung, 2001, Differential requirement for SLP-76 domains in T cell development and function, Immunity, 15, 1011, 10.1016/S1074-7613(01)00253-9 · DOI
- Yablonski, 2001, Identification of a phospholipase C-gamma1 (PLC-gamma1) SH3 domain-binding site in SLP-76 required for T-cell receptor-mediated activation of PLC-gamma1 and NFAT, Mol. Cell. Biol., 21, 4208, 10.1128/MCB.21.13.4208-4218.2001 · DOI
- Schaeper, 2000, Coupling of Gab1 to c-Met, Grb2, and Shp2 mediates biological responses, J. Cell Biol., 149, 1419, 10.1083/jcb.149.7.1419 · DOI
- Kato, 2000, A deubiquitinating enzyme UBPY interacts with the Src homology 3 domain of Hrs-binding protein via a novel binding motif PX(V/I)(D/N)RXXKP, J. Biol. Chem., 275, 37481, 10.1074/jbc.M007251200 · DOI · Paper page
- Nash, 2001, Multisite phosphorylation of a CDK inhibitor sets a threshold for the onset of DNA replication, Nature, 414, 514, 10.1038/35107009 · DOI
- van der Geer, 1996, The Shc adaptor protein is highly phosphorylated at conserved, twin tyrosine residues (Y239/240) that mediate protein-protein interactions, Curr. Biol., 6, 1435, 10.1016/S0960-9822(96)00748-8 · DOI
Cited by
Sorted by citations
Structure and regulation of Src family kinases
Boggon, T. J., & Eck, M. J. (2004) · Oncogene · doi:10.1038/sj.onc.1208081 · Cited by 712
Berlin, I., Schwartz, H., & Nash, P. D. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.016287 · Cited by 121
Self-citationLiu, H., Purbhoo, M. A., Davis, D. M., & Rudd, C. E. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909112107 · Cited by 18
Metadata
- Authors
- Berry, D. M., Nash, P., Liu, S. K.-W., Pawson, T., & McGlade, C. J.
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2002-08
- Volume
- 12
- Issue
- 15
- Pages
- 1336-1341
- ISSN
- 0960-9822
- Cited by
- 120
- References
- 0
- Language
- en
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
