scholarly journals SH2 Domain Function Is Essential for the Role of the Lck Tyrosine Kinase in T Cell Receptor Signal Transduction

1996 ◽  
Vol 271 (17) ◽  
pp. 9976-9981 ◽  
Author(s):  
David B. Straus ◽  
Andrew C. Chan ◽  
Barbara Patai ◽  
Arthur Weiss
Keyword(s):  
Signal Transduction ◽  
T Cell ◽  
Tyrosine Kinase ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Sh2 Domain ◽  
Receptor Signal

scholarly journals A therapeutic anti-CD4 monoclonal antibody inhibits T cell receptor signal transduction in mouse autoimmune cardiomyopathy

2007 ◽  
Vol 120 (15) ◽  
pp. 1319-1325 ◽  
Author(s):  
Zhao-hui WANG ◽  
Yu-hua LIAO ◽  
Jing YUAN ◽  
Li ZHANG ◽  
Min WANG ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Monoclonal Antibody ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Signal

scholarly journals Phase separation of signaling molecules promotes T cell receptor signal transduction

Science ◽  
2016 ◽  
Vol 352 (6285) ◽  
pp. 595-599 ◽  
Author(s):  
Xiaolei Su ◽  
Jonathon A. Ditlev ◽  
Enfu Hui ◽  
Wenmin Xing ◽  
Sudeep Banjade ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Phase Separation ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Signaling Molecules ◽  
Receptor Signal

scholarly journals Hypoxia inducible factor 1  regulates T cell receptor signal transduction

2005 ◽  
Vol 102 (47) ◽  
pp. 17071-17076 ◽  
Author(s):  
A. K. Neumann ◽  
J. Yang ◽  
M. P. Biju ◽  
S. K. Joseph ◽  
R. S. Johnson ◽  
...  
Keyword(s):  
Signal Transduction ◽  
T Cell ◽  
T Cell Receptor ◽  
Hypoxia Inducible Factor ◽  
Cell Receptor ◽  
Hypoxia Inducible Factor 1 ◽  
Receptor Signal

scholarly journals Identification, cloning, and characterization of a novel human T-cell- specific tyrosine kinase located at the hematopoietin complex on chromosome 5q

Blood ◽  
1993 ◽  
Vol 82 (5) ◽  
pp. 1561-1572 ◽  
Author(s):  
S Gibson ◽  
B Leung ◽  
JA Squire ◽  
M Hill ◽  
N Arima ◽  
...  
Keyword(s):  
Signal Transduction ◽  
T Cell ◽  
T Lymphocytes ◽  
Tyrosine Kinase ◽  
Tyrosine Phosphorylation ◽  
T Cell Receptor ◽  
Tyrosine Kinases ◽  
Phosphorylation Site ◽  
Cell Receptor ◽  
Cytokine Receptors

Signal transduction through the T-cell receptor and cytokine receptors on the surface of T lymphocytes occurs largely via tyrosine phosphorylation of intracellular substrates. Because neither the T-cell receptor nor cytokine receptors contain intrinsic kinase domains, signal transduction is thought to occur via association of these receptors with intracellular protein tyrosine kinases. Although several members of the SRC and SYK families of tyrosine kinases have been implicated in signal transduction in lymphocytes, it seems likely that additional tyrosine kinases involved in signal transduction remain to be identified. To identify unique T-cell tyrosine kinases, we used polymerase chain reaction-based cloning with degenerate oligonucleotides directed at highly conserved motifs of tyrosine kinase domains. We have cloned the complete cDNA for a unique human tyrosine kinase that is expressed mainly in T lymphocytes (EMT) and natural killer (NK) cells. The cDNA of EMT predicts an open reading frame of 1866 bp encoding a protein with a predicted size of 72 Kd, which is in keeping with its size on Western blotting. A single 6.2-kb EMT mRNA and 72-Kd protein were detected in T lymphocytes and NK-like cell lines, but were not detected in other cell lineages. EMT contains both SH2 and SH3 domains, as do many other intracellular kinases. EMT does not contain the N-terminal myristylation site or the negative regulatory tyrosine phosphorylation site in its carboxyterminus that are found in the SRC family of tyrosine kinases. EMT is related to the B-cell progenitor kinase (BPK), which has recently been implicated in X-linked hypogammaglobulinemia, to the TECI mammalian kinase, which has been implicated in liver neoplasia, to the more widely expressed TECII mammalian kinase, and to the Drosophila melanogaster Dsrc28 kinase. Sequence comparison suggests that EMT is likely the human homologue of a recently identified murine interleukin-2 (IL-2)-inducible T cell kinase (ITK). However, unlike ITK, EMT message and protein levels do not vary markedly on stimulation of human IL-2-responsive T cells with IL-2. Taken together, it seems that EMT is a member of a new family of intracellular kinases that includes BPK, TECI, and TECII. EMT was localized to chromosome 5q31–32, a region that contains the genes for several growth factors and receptors as well as early activation genes, particularly those involved in the hematopoietic system. Furthermore, the 5q31–32 region is implicated in the genesis of the 5q- syndrome associated with myelodysplasia and development of leukemia.(ABSTRACT TRUNCATED AT 400 WORDS)

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 ◽  
...  
Keyword(s):  
Signal Transduction ◽  
T Cell ◽  
T Cell Receptor ◽  
Protein Tyrosine Kinase ◽  
Adaptor Protein ◽  
Cell Receptor ◽  
Downstream Signaling ◽  
Cysteine Motif ◽  
Receptor Signal ◽  
Tcr Signal Transduction

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.

scholarly journals Allelic Exclusion of the T Cell Receptor β Locus Requires the Sh2 Domain–Containing Leukocyte Protein (Slp)-76 Adaptor Protein

1999 ◽  
Vol 190 (8) ◽  
pp. 1093-1102 ◽  
Author(s):  
Iannis Aifantis ◽  
Vadim I. Pivniouk ◽  
Frank Gärtner ◽  
Jacqueline Feinberg ◽  
Wojciech Swat ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Adaptor Protein ◽  
Cell Receptor ◽  
Sh2 Domain ◽  
Allelic Exclusion ◽  
Double Positive ◽  
Thymic Development ◽  
Developmental Progression

Signaling via the pre-T cell receptor (TCR) is required for the proliferative expansion and maturation of CD4−CD8− double-negative (DN) thymocytes into CD4+CD8+ double-positive (DP) cells and for TCR-β allelic exclusion. The adaptor protein SH2 domain–containing leukocyte protein (SLP)-76 has been shown to play a crucial role in thymic development, because thymocytes of SLP-76−/− mice are arrested at the CD25+CD44− DN stage. Here we show that SLP-76−/− DN thymocytes express the pre-TCR on their surfaces and that introduction of a TCR-α/β transgene into the SLP-76−/− background fails to cause expansion of DN thymocytes or developmental progression to the DP stage. Moreover, analysis of TCR-β rearrangement in SLP-76−/− TCR-transgenic mice or in single CD25+CD44− DN cells from SLP-76−/− mice indicates an essential role of SLP-76 in TCR-β allelic exclusion.

scholarly journals Inhibition of T Cell Receptor Signal Transduction by Tyrosine Kinase–interacting Protein of Herpesvirus saimiri

2004 ◽  
Vol 200 (5) ◽  
pp. 681-687 ◽  
Author(s):  
Nam-Hyuk Cho ◽  
Pinghui Feng ◽  
Sun-Hwa Lee ◽  
Bok-Soo Lee ◽  
Xiaozhen Liang ◽  
...  
Keyword(s):  
Signal Transduction ◽  
T Cells ◽  
T Cell ◽  
Tyrosine Kinase ◽  
T Cell Receptor ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cell Receptor ◽  
Herpesvirus Saimiri ◽  
Interacting Protein

T cells play a central role in orchestrating immunity against pathogens, particularly viruses. Thus, impairing T cell activation is an important strategy employed by viruses to escape host immune control. The tyrosine kinase–interacting protein (Tip) of the T lymphotropic Herpesvirus saimiri (HVS) is constitutively present in lipid rafts and interacts with cellular Lck tyrosine kinase and p80 endosomal protein. Here we demonstrate that, due to the sequestration of Lck by HVS Tip, T cell receptor (TCR) stimulation fails to activate ZAP70 tyrosine kinase and to initiate downstream signaling events. TCR ζ chains in Tip-expressing T cells were initially phosphorylated to recruit ZAP70 molecule upon TCR stimulation, but the recruited ZAP70 kinase was not subsequently phosphorylated, resulting in TCR complexes that were stably associated with inactive ZAP70 kinase. Consequently, Tip expression not only markedly inhibited TCR-mediated intracellular signal transduction but also blocked TCR engagement with major histocompatibility complexes on the antigen-presenting cells and immunological synapse formation. These results demonstrate that a lymphotropic herpesvirus has evolved a novel mechanism to deregulate T cell activation to disarm host immune surveillance. This process contributes to the establishment and maintenance of viral latency.

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