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 › peer-review

12 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
State	Published - Aug 2006

Keywords

LAT
Lck
PTB
SH2
SH3
Shc
TCR
ZAP-70

ASJC Scopus subject areas

Cell Biology

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10.1016/j.cellsig.2005.09.008

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title = "Lck couples Shc to TCR signaling",

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.",

keywords = "LAT, Lck, PTB, SH2, SH3, Shc, TCR, ZAP-70",

author = "Atsuki Fukushima and Yasue Hatanaka and Chang, {Jing Wen} and Masako Takamatsu and Nagendra Singh and Makio Iwashima",

note = "Funding Information: We thank Drs. A. Weiss and R. Abraham for reagents, and R. Markowitz for critical reading of this manuscript. A.F. was supported by the Japanese Ministry of Science and Education. This work was supported by grants from NIH for MI (AI 055022, AI049398).",

year = "2006",

month = aug,

doi = "10.1016/j.cellsig.2005.09.008",

language = "English (US)",

volume = "18",

pages = "1182--1189",

journal = "Cellular Signalling",

issn = "0898-6568",

publisher = "Elsevier Inc.",

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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

N1 - Funding Information: We thank Drs. A. Weiss and R. Abraham for reagents, and R. Markowitz for critical reading of this manuscript. A.F. was supported by the Japanese Ministry of Science and Education. This work was supported by grants from NIH for MI (AI 055022, AI049398).

PY - 2006/8

Y1 - 2006/8

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

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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 -

Lck couples Shc to TCR signaling

Abstract

Keywords

ASJC Scopus subject areas

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