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Itk: the rheostat of the T cell response.

Grasis JA, Tsoukas CD - J Signal Transduct (2011)

Bottom Line: The functional cellular outcome of these molecular regulations by Itk renders it an important mediator of T cell development and differentiation.This paper encompasses the structure of Itk, the signaling parameters leading to Itk activation, and Itk effects on molecular pathways resulting in functional cellular outcomes.The incorporation of these factors persuades one to believe that Itk serves as a modulator, or rheostat, critically fine-tuning the T cell response.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, San Diego State University, San Diego, CA 92182-4614, USA.

ABSTRACT
The nonreceptor tyrosine kinase Itk plays a key role in TCR-initiated signaling that directly and significantly affects the regulation of PLCĪ³1 and the consequent mobilization of Ca(2+). Itk also participates in the regulation of cytoskeletal reorganization as well as cellular adhesion, which is necessary for a productive T cell response. The functional cellular outcome of these molecular regulations by Itk renders it an important mediator of T cell development and differentiation. This paper encompasses the structure of Itk, the signaling parameters leading to Itk activation, and Itk effects on molecular pathways resulting in functional cellular outcomes. The incorporation of these factors persuades one to believe that Itk serves as a modulator, or rheostat, critically fine-tuning the T cell response.

No MeSH data available.


Related in: MedlinePlus

T cell receptor activated signal transduction pathways. Cartoon diagram of the critical protein interactions necessary for the activation of a T cell when engaging an antigen-presenting cell.
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Related In: Results  -  Collection


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fig1: T cell receptor activated signal transduction pathways. Cartoon diagram of the critical protein interactions necessary for the activation of a T cell when engaging an antigen-presenting cell.

Mentions: When a T cell encounters an antigen-presenting cell (APC), it must be able to discriminate whether or not the APC is functional. This occurs through physical interaction between surface molecules of the APC and T cell, translating that information into a response. This requires many coordinated molecular interactions from the cell surface, through the cytoplasm, on to the nucleus, and in some instances, back out through the cell surface again [1]. An illustration of this is shown in Figure 1. At the cell surface, interaction between the peptide-loaded major histocompatibility complex (pMHC) of class II or class I on the APC with the T cell receptor (TCR) on the T cell coordinates with coreceptor binding of CD4 on helper T cells or CD8 on cytotoxic T cells, respectively. This interaction causes the dissociation and activation of the tyrosine phosphatase CD45 from CD4/CD8, which dephosphorylates CD4/CD8 bound Src kinase Lck on its inhibitory tyrosine (tyrosine 505). With activated Lck in tow, CD4/CD8 co-receptor pulls Lck into proximity of the TCR/CD3 complex. Lck then phosphorylates the intracellular tyrosine activation motifs (ITAMs) within the CD3 complex. Phosphorylation of the CD3 ITAMs promotes the docking of other molecules to the CD3 complex, namely the zeta-associated protein of 70 kilodaltons (ZAP-70) which is also phosphorylated by Lck for its activation [2, 3]. Activated ZAP-70 then phosphorylates the linker for activated T cells, or LAT, a transmembrane and palmitoylated adaptor that bridges the initial TCR signal to many downstream signaling events [4].


Itk: the rheostat of the T cell response.

Grasis JA, Tsoukas CD - J Signal Transduct (2011)

T cell receptor activated signal transduction pathways. Cartoon diagram of the critical protein interactions necessary for the activation of a T cell when engaging an antigen-presenting cell.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3116522&req=5

fig1: T cell receptor activated signal transduction pathways. Cartoon diagram of the critical protein interactions necessary for the activation of a T cell when engaging an antigen-presenting cell.
Mentions: When a T cell encounters an antigen-presenting cell (APC), it must be able to discriminate whether or not the APC is functional. This occurs through physical interaction between surface molecules of the APC and T cell, translating that information into a response. This requires many coordinated molecular interactions from the cell surface, through the cytoplasm, on to the nucleus, and in some instances, back out through the cell surface again [1]. An illustration of this is shown in Figure 1. At the cell surface, interaction between the peptide-loaded major histocompatibility complex (pMHC) of class II or class I on the APC with the T cell receptor (TCR) on the T cell coordinates with coreceptor binding of CD4 on helper T cells or CD8 on cytotoxic T cells, respectively. This interaction causes the dissociation and activation of the tyrosine phosphatase CD45 from CD4/CD8, which dephosphorylates CD4/CD8 bound Src kinase Lck on its inhibitory tyrosine (tyrosine 505). With activated Lck in tow, CD4/CD8 co-receptor pulls Lck into proximity of the TCR/CD3 complex. Lck then phosphorylates the intracellular tyrosine activation motifs (ITAMs) within the CD3 complex. Phosphorylation of the CD3 ITAMs promotes the docking of other molecules to the CD3 complex, namely the zeta-associated protein of 70 kilodaltons (ZAP-70) which is also phosphorylated by Lck for its activation [2, 3]. Activated ZAP-70 then phosphorylates the linker for activated T cells, or LAT, a transmembrane and palmitoylated adaptor that bridges the initial TCR signal to many downstream signaling events [4].

Bottom Line: The functional cellular outcome of these molecular regulations by Itk renders it an important mediator of T cell development and differentiation.This paper encompasses the structure of Itk, the signaling parameters leading to Itk activation, and Itk effects on molecular pathways resulting in functional cellular outcomes.The incorporation of these factors persuades one to believe that Itk serves as a modulator, or rheostat, critically fine-tuning the T cell response.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, San Diego State University, San Diego, CA 92182-4614, USA.

ABSTRACT
The nonreceptor tyrosine kinase Itk plays a key role in TCR-initiated signaling that directly and significantly affects the regulation of PLCĪ³1 and the consequent mobilization of Ca(2+). Itk also participates in the regulation of cytoskeletal reorganization as well as cellular adhesion, which is necessary for a productive T cell response. The functional cellular outcome of these molecular regulations by Itk renders it an important mediator of T cell development and differentiation. This paper encompasses the structure of Itk, the signaling parameters leading to Itk activation, and Itk effects on molecular pathways resulting in functional cellular outcomes. The incorporation of these factors persuades one to believe that Itk serves as a modulator, or rheostat, critically fine-tuning the T cell response.

No MeSH data available.


Related in: MedlinePlus