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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jul 17, 2024 |
| Title |
A novel gain-of-function phosphorylation site modulates PTPN22 inhibition of TCR signaling |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Protein Tyrosine Phosphatase Non-receptor type 22 (PTPN22) is encoded by a major autoimmunity gene and is a known inhibitor of T cell receptor (TCR) signaling and drug target for cancer immunotherapy. However, little is known about PTPN22 post-translational regulation. Here we characterize a phosphorylation site at Ser325 situated C-terminal to the catalytic domain of PTPN22, and its roles in altering protein function. Signaling through the major TCR-dependent pathway under PTPN22 control was enhanced by CRISPR/Cas9 mediated suppression of Ser325 phosphorylation and inhibited by mimicking it via glutamic acid substitution. Next-generation sequencing (NGS) revealed it differentially regulates the expression of chemokines and T cell activation pathways. In conclusion, this study explores the function of a novel phosphorylation site of PTPN22 that is involved in complex regulation of TCR signaling .
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| Overall design |
We generated the CRISPR/Cas9 mediated mutagenesis of Ser325 to glutamic acid and Alanine to explore the roles of Ser325 phosphorylation in activated Jurkat T cells
The cells were starved and stimulated by antibodies against human CD3/CD28 antibodies for 16h, and cells were collected, washed and used for bulk RNA sequencing.
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| Contributor(s) |
Nunzio B, Shen Y, Richard A |
| Citation(s) |
38777143 |
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| Submission date |
Apr 19, 2024 |
| Last update date |
Jul 17, 2024 |
| Contact name |
Richard Ainsworth |
| E-mail(s) |
rainsworth05@gmail.com
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| Organization name |
Cedars-Sinai Medical Center
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| Street address |
8700 Beverly Blvd
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| City |
Los Angeles |
| ZIP/Postal code |
90048 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (24)
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| GSM8217139 |
S325A counterpart WT, Nonstimulated, biol rep 1 |
| GSM8217140 |
S325A counterpart WT, Nonstimulated, biol rep 2 |
| GSM8217141 |
S325A counterpart WT, Nonstimulated, biol rep 3 |
| GSM8217142 |
S325A mutant, Nonstimulated, biol rep 1 |
| GSM8217143 |
S325A mutant, Nonstimulated, biol rep 2 |
| GSM8217144 |
S325A mutant, Nonstimulated, biol rep 3 |
| GSM8217145 |
S325E counterpart WT, Nonstimulated, biol rep 1 |
| GSM8217146 |
S325E counterpart WT, Nonstimulated, biol rep 2 |
| GSM8217147 |
S325E counterpart WT, Nonstimulated, biol rep 3 |
| GSM8217148 |
S325E mutant, Nonstimulated, biol rep 1 |
| GSM8217149 |
S325E mutant, Nonstimulated, biol rep 2 |
| GSM8217150 |
S325E mutant, Nonstimulated, biol rep 3 |
| GSM8217151 |
S325A counterpart WT, CD3/CD28 stimulated, biol rep 1 |
| GSM8217152 |
S325A counterpart WT, CD3/CD28 stimulated, biol rep 2 |
| GSM8217153 |
S325A counterpart WT, CD3/CD28 stimulated, biol rep 3 |
| GSM8217154 |
S325A mutant, CD3/CD28 stimulated, biol rep 1 |
| GSM8217155 |
S325A mutant, CD3/CD28 stimulated, biol rep 2 |
| GSM8217156 |
S325A mutant, CD3/CD28 stimulated, biol rep 3 |
| GSM8217157 |
S325E conterpart WT, CD3/CD28 stimulated, biol rep 1 |
| GSM8217158 |
S325E conterpart WT, CD3/CD28 stimulated, biol rep 2 |
| GSM8217159 |
S325E conterpart WT, CD3/CD28 stimulated, biol rep 3 |
| GSM8217160 |
S325E mutant, CD3/CD28 stimulated, biol rep 1 |
| GSM8217161 |
S325E mutant, CD3/CD28 stimulated, biol rep 2 |
| GSM8217162 |
S325E mutant, CD3/CD28 stimulated, biol rep 3 |
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| Relations |
| BioProject |
PRJNA1102292 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE264373_count_matrix.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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