Src homology 2-containing protein tyrosine phosphatase 2 (SHP-2) is known to protect neurons from neurodegeneration during ischemia/reperfusion injury. We recently reported that ROS-mediated oxidative stress promotes phosphorylation of endogenous SHP-2 in astrocytes and complex formation between caveolin-1 and SHP-2 in response to oxidative stress. To examine the region of SHP-2 participating in complex formation with caveolin-1, we generated three deletion mutant constructs and six point mutation constructs of SHP-2. Compared with wild-type SHP-2, binding of the N-SH2 domain deletion mutant of SHP-2 to p-caveolin-1 was reduced greatly, using flow cytometric competitive binding assays and surface plasmon resonance (SPR). Moreover, deletion of the N-SH2 domain of SHP-2 affected H2O2-mediated ERK phosphorylation and Src phosphorylation at Tyr 419 in primary astrocytes, suggesting that N-SH2 domain of SHP-2 is responsible for the binding of caveolin-1 and contributes to the regulation of Src phosphorylation and activation following ROS-induced oxidative stress in brain astrocytes.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453023 | PMC |
http://dx.doi.org/10.5483/bmbrep.2015.48.3.249 | DOI Listing |
Leuk Lymphoma
January 2025
National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
Alterations in the RAS pathway underscore the pathogenic complexity of acute myeloid leukemia (AML), yet the full spectrum, including , , , , and , remains to be fully elucidated. In this retrospective study of 735 adult AML patients, the incidence of RAS pathway alterations was 32.4%, each with distinct clinical characteristics.
View Article and Find Full Text PDFZhongguo Shi Yan Xue Ye Xue Za Zhi
August 2024
Department of Hematology, Wuxi Second People's Hospital, Wuxi 214001, Jiangsu Province, China.
Objective: To investigate the incidence of gene mutation and its associated gene mutations in adult patients with acute myeloid leukemia (AML), and analyze its clinical characteristics.
Methods: Second-generation sequencing and Sanger sequencing were used to detect 51 gene mutations, and multiplex-PCR was used to detect 41 fusion genes from 451 newly diagnosed adult AML patients admitted to Affiliated Hospital of Jiangnan University, Changzhou Second People's Hospital, Wuxi People's Hospital and Wuxi Second People's Hospital from January 2017 to July 2022.
Results: Among 451 primary adult AML patients, the gene mutation was detected in 34 cases, and the mutation rate was 7.
Proc Natl Acad Sci U S A
July 2024
Department of Chemistry, Columbia University, New York, NY 10027.
Mutations in the tyrosine phosphatase Src homology-2 domain-containing protein tyrosine phosphatase-2 (SHP2) are associated with a variety of human diseases. Most mutations in SHP2 increase its basal catalytic activity by disrupting autoinhibitory interactions between its phosphatase domain and N-terminal SH2 (phosphotyrosine recognition) domain. By contrast, some disease-associated mutations located in the ligand-binding pockets of the N- or C-terminal SH2 domains do not increase basal activity and likely exert their pathogenicity through alternative mechanisms.
View Article and Find Full Text PDFMol Divers
October 2024
Department of Bioengineering, Faculty of Life and Natural Sciences, Abdullah Gül University, 38080, Kayseri, Türkiye.
There are many genes that produce proteins related to diseases and these proteins can be targeted with drugs as a potential therapeutic approach. Recent advancement in drug discovery techniques have created new opportunities for treating variety of diseases by targeting disease-related proteins. Structure-based drug discovery is a faster and more cost-effective approach than traditional methods.
View Article and Find Full Text PDFComput Struct Biotechnol J
December 2024
Theoretical Physics and Center for Biophysics, Saarland University, 66123 Saarbrücken, Germany.
SHP2 is a tyrosine phosphatase that plays a regulatory role in multiple intracellular signaling cascades and is known to be oncogenic in certain contexts. In the absence of effectors, SHP2 adopts an autoinhibited conformation with its N-SH2 domain blocking the active site. Given the key role of N-SH2 in regulating SHP2, this domain has been extensively studied, often by X-ray crystallography.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!