hnRNPA1 的 AKT 磷酸化调节 T 细胞的命运和功能-猫眼课题宝

hnRNPA1 的 AKT 磷酸化调节 T 细胞的命运和功能

批准号：

10455605

负责人：

Tristan Augustus Lenora White

金额：

$2.04万

依托单位：

UNIVERSITY OF PITTSBURGH AT PITTSBURGH

依托单位国家：

美国

项目类别：

财政年份：

2020

资助国家：

美国

项目状态：

已结题

起止时间：

2020-08-01 至 2023-03-31

来源：

https://reporter.nih.gov/project-details/10455605

关键词：

Affect Affinity Alanine Alternative Splicing Animal Model Antigens Autoantigens Autoimmune Diseases Autoimmunity Biogenesis CD4 Positive T Lymphocytes Cell Differentiation process Cells Cellular Metabolic Process Cellular biology Data Development Disease Dose Eragrostis Event FOXO1A gene FRAP1 gene Gene Expression Growth Heterogeneous-Nuclear Ribonucleoprotein L Heterogeneous-Nuclear Ribonucleoproteins Immune Immunotherapy Impairment Inflammatory Inflammatory Bowel Diseases Investigation Lead Malignant Neoplasms Mediating Mus Mutant Strains Mice Mutate Mutation PTEN gene Pathway interactions Peripheral Phosphorylation Phosphorylation Site Play Population Positioning Attribute Process Proto-Oncogene Proteins c-akt RNA RNA Processing RNA Splicing RNA Stability RNA-Binding Proteins Regulator Genes Regulatory T-Lymphocyte Research Role Self Tolerance Serine Signal Pathway Signal Transduction Small Interfering RNA Substrate Specificity System T cell differentiation T-Lymphocyte Thymus Gland Transcript base disorder control experimental study interest knock-down mTOR Signaling Pathway migration mouse model mutant mutant mouse model novel overexpression prevent response targeted treatment therapy development

项目摘要

项目成果

Tristan Augustus Lenora White的其他基金

相似基金

相关文献

中文摘要

翻译

点击翻译按钮获取中文摘要

英文摘要

AKT phosphorylation of hnRNPA1 and hnRNPL modulates T cell fate and function Regulatory T cells (Treg) play a significant role in maintaining self-tolerance and preventing autoimmune diseases. We and others have shown that low dose favors Treg and T helper (Th) 2 cell differentiation, while high Ag dose stimulation activates the PI3K/Akt/mTOR pathway, favoring inflammatory Th1 and Th17 cell differentiation (Teff). Differences in PI3K/Akt/mTOR signaling not only affect T cell fate but our research shows that Akt phosphorylation of the RNA-binding protein, (RBP) heterogeneous nuclear ribonucleoprotein (hnRNP) A1, is dependent on TCR signal strength. RBPs such as hnRNPA1 are emerging as regulators of RNA processing and stability in immune cells, and the effect of RBP on T cell differentiation is a growing subject of interest. We have shown hnRNPA1 is required for optimal Treg differentiation by performing knockdown experiments, and that it is phosphorylated by Akt following low dose stimulation. Our present research is focused on identifying a role for Akt phosphorylation in hnRNPA1 function. HnRNPA1 is known to have a single Akt phosphorylation site at S199 and our lab has generated a new mutant mouse model, hnRNPA1-S199A (mA1). This mutation affects the ability of Akt to phosphorylate hnRNPA1 in all immune cells. Preliminary data suggest that Treg differentiation induced by low TCR stimulation is impaired in the T cells from the mutant mouse. Based on these preliminary findings we hypothesize that Akt-mediated phosphorylation of hnRNPL and/or hnRNPA1 upon low TCR stimulation controls the processing of RNA transcripts involved in Treg differentiation. The following specific aims are proposed; 1) To determine how the hnRNPA1-S199A mutation affects T cell fate and function. 2) To determine the impact hnRNPA1 has on RNA splicing and stability. 3) To identify the AKT phosphorylation site on hnRNPL. 4)To determine how hnRNPL effects T cell fate and function.

期刊论文(1)

专著(0)

科研奖励(0)

会议论文

AKT phosphorylation of hnRNPA1 modulates T cell fate and function

批准号：

10316980
项目类别：
资助金额：

$4.6万
财政年份：

2020
负责人：

Tristan Augustus Lenora White
依托单位：

UNIVERSITY OF PITTSBURGH AT PITTSBURGH

海外基金