scholarly journals Association of the Adaptor Molecule Lat with Cd4 and Cd8 Coreceptors Identifies a New Coreceptor Function in T Cell Receptor Signal Transduction

1999 ◽  
Vol 190 (10) ◽  
pp. 1517-1526 ◽  
Author(s):  
Rémy Bosselut ◽  
Weiguo Zhang ◽  
Jennifer M. Ashe ◽  
Jeffrey L. Kopacz ◽  
Lawrence E. Samelson ◽  
...  

Linker for activation of T cells (LAT) is an adaptor protein whose tyrosine phosphorylation is critical for transduction of the T cell receptor (TCR) signal. LAT phosphorylation is accomplished by the protein tyrosine kinase ZAP-70, but it is not at all clear how LAT (which is not associated with the TCR) encounters ZAP-70 (which is bound to the TCR). Here we show that LAT associates with surface CD4 and CD8 coreceptors and that its association is promoted by the same coreceptor cysteine motif that mediates Lck binding. In fact, LAT competes with Lck for binding to individual coreceptor molecules but differs from Lck in its preferential association with CD8 rather than CD4 in CD4+CD8+ thymocytes. Importantly, as a consequence of LAT association with surface coreceptors, coengagement of the TCR with surface coreceptors induces LAT phosphorylation and the specific recruitment of downstream signaling mediators to coreceptor-associated LAT molecules. These results point to a new function for CD4 and CD8 coreceptors in TCR signal transduction, namely to promote LAT phosphorylation by ZAP-70 by recruiting LAT to major histocompatibility complex–engaged TCR complexes.

2004 ◽  
Vol 24 (12) ◽  
pp. 5369-5382 ◽  
Author(s):  
Sun-Hwa Lee ◽  
Young-Hwa Chung ◽  
Nam-Hyuk Cho ◽  
Yousang Gwack ◽  
Pinghui Feng ◽  
...  

ABSTRACT Because of its central regulatory role, T-cell receptor (TCR) signal transduction is a common target of viruses. We report here the identification of a small signaling protein, ORF5, of the T-lymphotropic tumor virus herpesvirus saimiri (HVS). ORF5 is predicted to contain 89 to 91 amino acids with an amino-terminal myristoylation site and six SH2 binding motifs, showing structural similarity to cellular LAT (linker for activation of T cells). Sequence analysis showed that, despite extensive sequence variation, the myristoylation site and SH2 binding motifs were completely conserved among 13 different ORF5 isolates. Upon TCR stimulation, ORF5 was efficiently tyrosine phosphorylated and subsequently interacted with cellular SH2-containing signaling proteins Lck, Fyn, SLP-76, and p85 through its tyrosine residues. ORF5 expression resulted in the marked augmentation of TCR signal transduction activity, evidenced by increased cellular tyrosine phosphorylation, intracellular calcium mobilization, CD69 surface expression, interleukin-2 production, and activation of the NF-AT, NF-κB, and AP-1 transcription factors. Despite its structural similarity to cellular LAT, however, ORF5 could only partially substitute for LAT function in TCR signal transduction. These results demonstrate that HVS utilizes a novel signaling protein, ORF5, to activate TCR signal transduction. This activation probably facilitates viral gene expression and, thereby, persistent infection.


2007 ◽  
Vol 120 (15) ◽  
pp. 1319-1325 ◽  
Author(s):  
Zhao-hui WANG ◽  
Yu-hua LIAO ◽  
Jing YUAN ◽  
Li ZHANG ◽  
Min WANG ◽  
...  

Science ◽  
2016 ◽  
Vol 352 (6285) ◽  
pp. 595-599 ◽  
Author(s):  
Xiaolei Su ◽  
Jonathon A. Ditlev ◽  
Enfu Hui ◽  
Wenmin Xing ◽  
Sudeep Banjade ◽  
...  

2005 ◽  
Vol 102 (47) ◽  
pp. 17071-17076 ◽  
Author(s):  
A. K. Neumann ◽  
J. Yang ◽  
M. P. Biju ◽  
S. K. Joseph ◽  
R. S. Johnson ◽  
...  

2018 ◽  
Vol 19 ◽  
pp. 43-50 ◽  
Author(s):  
Duane Moogk ◽  
Aswin Natarajan ◽  
Michelle Krogsgaard

2016 ◽  
Vol 213 (5) ◽  
pp. 501-503 ◽  
Author(s):  
Michael L. Dustin ◽  
Lance C. Kam

Mechanical forces play increasingly recognized roles in T cell receptor (TCR) signal transduction. Hu and Butte (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201511053) demonstrate that actin is required for T cells to generate forces at the TCR and that exogenous application of force can emulate these cytoskeletal forces and trigger T cell activation.


1996 ◽  
Vol 271 (17) ◽  
pp. 9976-9981 ◽  
Author(s):  
David B. Straus ◽  
Andrew C. Chan ◽  
Barbara Patai ◽  
Arthur Weiss

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