Abstract
Recent genetic evidence demonstrated that Shc is a critical molecule for T cell activation and differentiation. However, how Shc is coupled to the T cell antigen receptor (TCR) has not been clearly characterized. Here we report that the tyrosine kinase Lck functions as a connecting molecule for TCR and Shc. Lck plays a critical role in TCR signal transduction by phosphorylating the immuno-receptor tyrosine based activation motif (ITAM). Our data shows that the PTB domain of Shc binds the SH2/3 domains of Lck in a phosphotyrosine-independent manner. Inhibition of the Lck/Shc interaction led to the loss of IL-2 promoter activation, confirming that the role of Shc in IL-2 production requires its interaction with Lck. Together, the data show that Shc is connected to the activated TCR via direct interaction with Lck.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1182-1189 |
| Number of pages | 8 |
| Journal | Cellular Signalling |
| Volume | 18 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 1 2006 |
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Keywords
- LAT
- Lck
- PTB
- SH2
- SH3
- Shc
- TCR
- ZAP-70
ASJC Scopus subject areas
- Cell Biology
Cite this
Lck couples Shc to TCR signaling. / Fukushima, Atsuki; Hatanaka, Yasue; Chang, Jing Wen; Takamatsu, Masako; Singh, Nagendra; Iwashima, Makio.
In: Cellular Signalling, Vol. 18, No. 8, 01.08.2006, p. 1182-1189.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Lck couples Shc to TCR signaling
AU - Fukushima, Atsuki
AU - Hatanaka, Yasue
AU - Chang, Jing Wen
AU - Takamatsu, Masako
AU - Singh, Nagendra
AU - Iwashima, Makio
PY - 2006/8/1
Y1 - 2006/8/1
N2 - Recent genetic evidence demonstrated that Shc is a critical molecule for T cell activation and differentiation. However, how Shc is coupled to the T cell antigen receptor (TCR) has not been clearly characterized. Here we report that the tyrosine kinase Lck functions as a connecting molecule for TCR and Shc. Lck plays a critical role in TCR signal transduction by phosphorylating the immuno-receptor tyrosine based activation motif (ITAM). Our data shows that the PTB domain of Shc binds the SH2/3 domains of Lck in a phosphotyrosine-independent manner. Inhibition of the Lck/Shc interaction led to the loss of IL-2 promoter activation, confirming that the role of Shc in IL-2 production requires its interaction with Lck. Together, the data show that Shc is connected to the activated TCR via direct interaction with Lck.
AB - Recent genetic evidence demonstrated that Shc is a critical molecule for T cell activation and differentiation. However, how Shc is coupled to the T cell antigen receptor (TCR) has not been clearly characterized. Here we report that the tyrosine kinase Lck functions as a connecting molecule for TCR and Shc. Lck plays a critical role in TCR signal transduction by phosphorylating the immuno-receptor tyrosine based activation motif (ITAM). Our data shows that the PTB domain of Shc binds the SH2/3 domains of Lck in a phosphotyrosine-independent manner. Inhibition of the Lck/Shc interaction led to the loss of IL-2 promoter activation, confirming that the role of Shc in IL-2 production requires its interaction with Lck. Together, the data show that Shc is connected to the activated TCR via direct interaction with Lck.
KW - LAT
KW - Lck
KW - PTB
KW - SH2
KW - SH3
KW - Shc
KW - TCR
KW - ZAP-70
UR - http://www.scopus.com/inward/record.url?scp=33646368919&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646368919&partnerID=8YFLogxK
U2 - 10.1016/j.cellsig.2005.09.008
DO - 10.1016/j.cellsig.2005.09.008
M3 - Article
C2 - 16257509
AN - SCOPUS:33646368919
VL - 18
SP - 1182
EP - 1189
JO - Cellular Signalling
JF - Cellular Signalling
SN - 0898-6568
IS - 8
ER -