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
State	Published - Aug 1 2006

Keywords

LAT
Lck
PTB
SH2
SH3
Shc
TCR
ZAP-70

ASJC Scopus subject areas

Cell Biology

Access to Document

10.1016/j.cellsig.2005.09.008

Fingerprint Dive into the research topics of 'Lck couples Shc to TCR signaling'. Together they form a unique fingerprint.

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

@article{6eaa1d51bb6542e5b1fe80709d15d937,

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",

year = "2006",

month = aug,

day = "1",

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.",

number = "8",

}

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 -