Abstract
T cell antigen receptor (TCR)-mediated activation of T cells requires the interaction of dozens of proteins. Here we used quantitative mass spectrometry and activated primary CD4 + T cells from mice in which a tag for affinity purification was knocked into several genes to determine the composition and dynamics of multiprotein complexes that formed around the kinase Zap70 and the adaptors Lat and SLP-76. Most of the 112 high-confidence time-resolved protein interactions we observed were previously unknown. The surface receptor CD6 was able to initiate its own signaling pathway by recruiting SLP-76 and the guanine nucleotide-exchange factor Vav1 regardless of the presence of Lat. Our findings provide a more complete model of TCR signaling in which CD6 constitutes a signaling hub that contributes to the diversification of TCR signaling.
| Original language | English |
|---|---|
| Pages (from-to) | 384-392 |
| Number of pages | 9 |
| Journal | Nature Immunology |
| Volume | 15 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 2014 |
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All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Immunology
Cite this
Quantitative proteomics analysis of signalosome dynamics in primary T cells identifies the surface receptor CD6 as a Lat adaptor-independent TCR signaling hub. / Roncagalli, Romain; Hauri, Simon; Fiore, Fréderic; Liang, Yinming; Chen, Zhi; Sansoni, Amandine; Kanduri, Kartiek; Joly, Rachel; Malzac, Aurélie; Lähdesmäki, Harri; Lahesmaa, Riitta; Yamasaki, Sho; Saito, Takashi; Malissen, Marie; Aebersold, Ruedi; Gstaiger, Matthias; Malissen, Bernard.
In: Nature Immunology, Vol. 15, No. 4, 04.2014, p. 384-392.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Quantitative proteomics analysis of signalosome dynamics in primary T cells identifies the surface receptor CD6 as a Lat adaptor-independent TCR signaling hub
AU - Roncagalli, Romain
AU - Hauri, Simon
AU - Fiore, Fréderic
AU - Liang, Yinming
AU - Chen, Zhi
AU - Sansoni, Amandine
AU - Kanduri, Kartiek
AU - Joly, Rachel
AU - Malzac, Aurélie
AU - Lähdesmäki, Harri
AU - Lahesmaa, Riitta
AU - Yamasaki, Sho
AU - Saito, Takashi
AU - Malissen, Marie
AU - Aebersold, Ruedi
AU - Gstaiger, Matthias
AU - Malissen, Bernard
PY - 2014/4
Y1 - 2014/4
N2 - T cell antigen receptor (TCR)-mediated activation of T cells requires the interaction of dozens of proteins. Here we used quantitative mass spectrometry and activated primary CD4 + T cells from mice in which a tag for affinity purification was knocked into several genes to determine the composition and dynamics of multiprotein complexes that formed around the kinase Zap70 and the adaptors Lat and SLP-76. Most of the 112 high-confidence time-resolved protein interactions we observed were previously unknown. The surface receptor CD6 was able to initiate its own signaling pathway by recruiting SLP-76 and the guanine nucleotide-exchange factor Vav1 regardless of the presence of Lat. Our findings provide a more complete model of TCR signaling in which CD6 constitutes a signaling hub that contributes to the diversification of TCR signaling.
AB - T cell antigen receptor (TCR)-mediated activation of T cells requires the interaction of dozens of proteins. Here we used quantitative mass spectrometry and activated primary CD4 + T cells from mice in which a tag for affinity purification was knocked into several genes to determine the composition and dynamics of multiprotein complexes that formed around the kinase Zap70 and the adaptors Lat and SLP-76. Most of the 112 high-confidence time-resolved protein interactions we observed were previously unknown. The surface receptor CD6 was able to initiate its own signaling pathway by recruiting SLP-76 and the guanine nucleotide-exchange factor Vav1 regardless of the presence of Lat. Our findings provide a more complete model of TCR signaling in which CD6 constitutes a signaling hub that contributes to the diversification of TCR signaling.
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UR - http://www.scopus.com/inward/citedby.url?scp=84897046940&partnerID=8YFLogxK
U2 - 10.1038/ni.2843
DO - 10.1038/ni.2843
M3 - Article
C2 - 24584089
AN - SCOPUS:84897046940
VL - 15
SP - 384
EP - 392
JO - Nature Immunology
JF - Nature Immunology
SN - 1529-2908
IS - 4
ER -