Lck couples Shc to TCR signaling

Atsuki Fukushima; Yasue Hatanaka; Jing Wen Chang; Masako Takamatsu; Nagendra Singh; Makio Iwashima

doi:10.1016/j.cellsig.2005.09.008

Lck couples Shc to TCR signaling

Atsuki Fukushima, Yasue Hatanaka, Jing Wen Chang, Masako Takamatsu, Nagendra Singh, Makio Iwashima

Biochemistry and Molecular Biology

Research output: Contribution to journal › Article

11 Scopus citations

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	https://doi.org/10.1016/j.cellsig.2005.09.008
Publication status	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

Fukushima, A., Hatanaka, Y., Chang, J. W., Takamatsu, M., Singh, N., & Iwashima, M. (2006). Lck couples Shc to TCR signaling. Cellular Signalling, 18(8), 1182-1189. https://doi.org/10.1016/j.cellsig.2005.09.008

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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.",

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AU - Hatanaka, Yasue

AU - Chang, Jing Wen

AU - Takamatsu, Masako

AU - Singh, Nagendra

AU - Iwashima, Makio

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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.

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Access to Document

10.1016/j.cellsig.2005.09.008