We evaluated the role of Lck tyrosine kinase, an early effector of T cell activation, in regulation of the membrane-cytoskeleton linker protein ezrin. Ezrin was constitutively tyrosine phosphorylated in wild-type and CD45-deficient Jurkat T cells, but not in Lck-deficient cells. However, phosphorylation was evident in cells, in which Lck activity had been restored by transfection. Phosphorylation was reduced by the Src family kinase inhibitor PP2 and increased by the tyrosine phosphatase inhibitor pervanadate, implying continuous tyrosine phosphorylation and dephosphorylation. Lck phosphorylated ezrin in vitro, and the major phosphotyrosine was identified as Y145. These results identify ezrin as the first cytoskeletal substrate for Lck.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/s0014-5793(02)03861-9 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Pharmacoproteogenomic approach identifies on-target kinase inhibitors for cancer drug repositioning.
In Vitro Cell Dev Biol Anim
December 2024
Division of Rare Cancer Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.
Drug repositioning of approved drugs offers advantages over de novo drug development for a rare type of cancer. To efficiently identify on-target drugs from clinically successful kinase inhibitors in cancer drug repositioning, drug screening and molecular profiling of cell lines are essential to exclude off-targets. We developed a pharmacoproteogenomic approach to identify on-target kinase inhibitors, combining molecular profiling of genomic features and kinase activity, and drug screening of patient-derived cell lines.
View Article and Find Full Text PDFStudy on synthesis of ursodeoxycholic acid by reduction of 7-ketolithocholic acid in double aprotic solvents and molecular simulations.
Bioresour Bioprocess
August 2023
State Key Laboratory of Bioreactor Engineering, Department of Bioengineering, East China University of Science and Technology, Shanghai, 200237, China.
Article Synopsis
- Ursodeoxycholic acid (UDCA) is preferred over chenodeoxycholic acid for treating liver diseases and shows promise for Acute Kidney Injury and Parkinson's Disease; the study aims to enhance the production of UDCA from 7-ketocholic acid using specific solvents.
- Three aprotic solvents were tested to optimize the electrochemical reduction process, where 1,3-Dimethyl-2-imidazolidinone (DMI) proved stable and effective, while Hexamethylphosphoramide (HMPA) and DMPU had potential side reactions.
- Results indicated that using a Cu electrode with a mix of DMI and HMPA allowed for a 98% conversion rate of
THEMIS is a substrate and allosteric activator of SHP1, playing dual roles during T cell development.
Nat Struct Mol Biol
January 2024
School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
THEMIS plays an indispensable role in T cells, but its mechanism of action has remained highly controversial. Using the systematic proximity labeling methodology PEPSI, we identify THEMIS as an uncharacterized substrate for the phosphatase SHP1. Saturated mutagenesis assays and mass spectrometry analysis reveal that phosphorylation of THEMIS at the evolutionally conserved Tyr34 residue is oppositely regulated by SHP1 and the kinase LCK.
View Article and Find Full Text PDFDiscovery of a selective TC-PTP degrader for cancer immunotherapy.
Chem Sci
November 2023
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University West Lafayette IN 47907 USA
T-cell protein tyrosine phosphatase (TC-PTP), encoded by PTPN2, has emerged as a promising target for cancer immunotherapy. TC-PTP deletion in B16 melanoma cells promotes tumor cell antigen presentation, while loss of TC-PTP in T-cells enhances T-cell receptor (TCR) signaling and stimulates cell proliferation and activation. Therefore, there is keen interest in developing TC-PTP inhibitors as novel immunotherapeutic agents.
View Article and Find Full Text PDFp38 MAPK involvement in the thermal stress response occurs via HSP27 and caspase3 in the large yellow croaker (Larimichthys crocea).
Comp Biochem Physiol B Biochem Mol Biol
January 2024
State Key Laboratory of Mariculture Breeding, Fisheries College, Jimei University, Xiamen 361021, China. Electronic address:
The p38 mitogen-activated protein kinase (p38 MAPK) is a multifunctional molecule that is involved in cellular response to various stressful stimuli. In the present study, the full-length cDNA sequence of p38 MAPK (Lcp38 MAPK) was identified from the large yellow croaker Larimichthys crocea, which encoded a polypeptide of 361 amino acid residues. The predicted Lcp38 MAPK protein contained a highly conserved Thr-Gly-Tyr (TGY) motif, a glutamate and aspartate (ED) site, a substrate binding site (Ala-Thr-Arg-Trp < ATRW>), and a serine/threonine kinase catalytic (S_TKc) domain characteristic of the MAPK family.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!