Negative Regulation Of T Cell Activation And Function By CIN85 Adaptor Protein

Simple item page
dc.contributor.authorKong, Mei Suen
dc.date.accessioned2019-08-01T02:32:06Z
dc.date.available2019-08-01T02:32:06Z
dc.date.issued2017-01
dc.description.abstractAntigen recognition by T cell receptor (TCR) induces intracellular signaling cascades leading to T cell activation, subsequently inducing cellular proliferation and various effector functions. Adaptor proteins play important roles in T cell signaling by creating nodes to recruit signaling proteins and form signal complexes to regulate the direction of signaling. Casitas B-lineage lymphoma (Cbl)-interacting protein of 85 kDa (CIN85) is an adaptor protein, originally identified as a Cbl-binding protein, and was suggested to be involved in the internalization and degradation of receptors and kinases. Nevertheless, the physiological function of CIN85 in T cells is unknown. To understand the role of CIN85 in T cell function, T cell-specific CIN85-knockout (KO) mice were generated and analyzed in this study. CIN85-KO naïve T cells were found to exhibit hyper-responsiveness to TCR stimulation; i.e. significantly increased interleukin 2 (IL-2) production, cell proliferation and alteration of differentiation into T helper type 1 (Th1) phenotypes, suggesting that CIN85 exhibits negative regulation in T cell activation. Analysis of signaling molecules showed that tyrosine phosphorylation of TCR-downstream molecules, such as ζ-chain associated protein kinase of 70 kDa (Zap70), SH2 domain-containing leukocyte protein of 76 kDa (SLP76), phospholipase C-gamma (PLCγ), c-Jun-N-terminal kinase (JNK) and extracellular-signal-regulated kinase (ERK), were significantly enhanced in CIN85-KO T cells. This implied that CIN85 was involved in the early TCR signaling complex to negatively regulate T cell activation. As for T cell development, CIN85-KO mice were found to display higher population of CD44hi effector/memory-type T cells at the periphery, suggesting an important role of CIN85 in maintaining the homeostasis of T cells in vivo.en_US
dc.identifier.urihttp://hdl.handle.net/123456789/8548
dc.language.isoenen_US
dc.publisherUniversiti Sains Malaysiaen_US
dc.subjectNegative regulation of T cell activationen_US
dc.subjectfunction by CIN85 adaptor proteinen_US
dc.titleNegative Regulation Of T Cell Activation And Function By CIN85 Adaptor Proteinen_US
dc.typeThesisen_US
Files
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Pusat Pengajian Sains Farmasi - Tesis