protein tyrosine
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2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Jai Prakash Singh ◽  
Yang Li ◽  
Yi-Yun Chen ◽  
Shang-Te Danny Hsu ◽  
Rebecca Page ◽  
...  

AbstractT-Cell Protein Tyrosine Phosphatase (TCPTP, PTPN2) is a non-receptor type protein tyrosine phosphatase that is ubiquitously expressed in human cells. TCPTP is a critical component of a variety of key signaling pathways that are directly associated with the formation of cancer and inflammation. Thus, understanding the molecular mechanism of TCPTP activation and regulation is essential for the development of TCPTP therapeutics. Under basal conditions, TCPTP is largely inactive, although how this is achieved is poorly understood. By combining biomolecular nuclear magnetic resonance spectroscopy, small-angle X-ray scattering, and chemical cross-linking coupled with mass spectrometry, we show that the C-terminal intrinsically disordered tail of TCPTP functions as an intramolecular autoinhibitory element that controls the TCPTP catalytic activity. Activation of TCPTP is achieved by cellular competition, i.e., the intrinsically disordered cytosolic tail of Integrin-α1 displaces the TCPTP autoinhibitory tail, allowing for the full activation of TCPTP. This work not only defines the mechanism by which TCPTP is regulated but also reveals that the intrinsically disordered tails of two of the most closely related PTPs (PTP1B and TCPTP) autoregulate the activity of their cognate PTPs via completely different mechanisms.


2022 ◽  
Author(s):  
Hai-ru Xu ◽  
Jun-jie Chen ◽  
Jin-ming Shen ◽  
Wei-hang Ding ◽  
Jie Chen

Abstract Objective: To explore the prognostic significance and underlying mechanism of TYRO protein tyrosine kinase-binding protein (TYROBP) in osteosarcoma. Methods: Firstly, the expression of TYROBP was analyzed using the t-test. The Kaplan-Meier plotter analysis and a receiver operating characteristic (ROC) curve were performed to evaluate the influence of TYROBP on overall survival (OS). Further, Cox regression analysis was conducted to predict the independent prognostic factors for OS of osteosarcoma patients, and a nomogram was constructed. Then, the relationship between TYROBP and clinicopathological characteristics was determined using statistical methods. Enrichment analyses were conducted to evaluate the biological functions of TYROBP. Finally, ESTIMATE algorithm was used to assess the association of TYROBP with immune cell infiltration. Results: TYROBP was significantly increased in osteosarcoma (all P <0.001). However, the high expression of TYROBP was related to better OS of osteosarcoma patients. Cox regression analysis showed that TYROBP was an independent prognostic factor for predicting OS (P =0.005), especially in patients with male sex, age <18 years, metastasis, and tumor site leg/foot (all P <0.05). Besides, TYROBP mRNA expression was significantly associated with tumor site (P <0.01) but had no remarkable relationship with age, gender, and metastasis status (all P>0.05). Functional annotation and GSEA revealed that TYROBP was mainly involved in immune-related pathways. Importantly, TYROBP positively correlated with immune scores (P <0.001, r=0.87). Conclusions: TYROBP served as an independent prognostic biomarker for OS in osteosarcoma. High TYROBP expression might prolong the survival of osteosarcoma patients mainly through promoting antitumor immunity.


Author(s):  
Christian Boni ◽  
Claudio Sorio

Members of the Protein Tyrosine Phosphatase (PTPs) family are associated with growth regulation and cancer development. Acting as natural counterpart of tyrosine kinases (TKs), mainly involved in crucial signaling pathways such as regulation of cell cycle, proliferation, invasion and angiogenesis, they represent key parts of complex physiological homeostatic mechanisms. Protein tyrosine phosphatase gamma (PTPRG) is classified as a R5 of the receptor type (RPTPs) subfamily and is broadly expressed in various isoforms in different tissues. PTPRG is considered a tumor-suppressor gene (TSG) mapped on chromosome 3p14-21, a region frequently subject to loss of heterozygosity in various tumors. However, reported mechanisms of PTPRG downregulation include missense mutations, ncRNA gene regulation and epigenetic silencing by hypermethylation of CpG sites on promoter region causing loss of function of the gene product. Inactive forms or total loss of PTPRG protein have been described in sporadic and Lynch syndrome colorectal cancer, nasopharyngeal carcinoma, ovarian, breast, and lung cancers, gastric cancer or diseases affecting the hematopoietic compartment as Lymphoma and Leukemia. Noteworthy, in Central Nervous System (CNS) PTPRZ/PTPRG appears to be crucial in maintaining glioblastoma cell-related neuronal stemness, carving out a pathological functional role also in this tissue. In this review, we will summarize the current knowledge on the role of PTPRG in various human cancers.


2022 ◽  
Author(s):  
Supapid Eknikom ◽  
Ryo Nasuno ◽  
Hiroshi Takagi

Abstract Protein tyrosine nitration (PTN), in which tyrosine (Tyr) residues on proteins are converted into 3-nitrotyrosine (NT), is one of the post-translational modifications mediated by reactive nitrogen species (RNS). Many recent studies have reported that PTN contributed to signaling systems by altering the structures and/or functions of proteins. This study aimed to investigate connections between PTN and the inhibitory effect of nitrite-derived RNS on fermentation ability using the yeast Saccharomyces cerevisiae. The results indicated that RNS inhibited the ethanol production of yeast cells with increased intracellular pyruvate content. We also found that RNS decreased the activities of pyruvate decarboxylase (PDC) as a critical enzyme involved in ethanol production. Our proteomic analysis revealed that the main PDC isozyme Pdc1 underwent the PTN modification at Tyr38, Tyr157, and Tyr344. The biochemical analysis using the recombinant purified Pdc1 enzyme indicated that PTN at Tyr157 or Tyr344 significantly reduced the Pdc1 activity. Interestingly, the substitution of Tyr157 or Tyr344 to phenylalanine, which is no longer converted into NT, recovered the ethanol production under the RNS treatment conditions. These findings suggest that nitrite impairs the fermentation ability of yeast by inhibiting the Pdc1 activity via its PTN modification at Tyr157 and Tyr344 of Pdc1.


2022 ◽  
Author(s):  
Jiao Kong ◽  
Yaqiu Long

Src homology 2 domain-containing protein tyrosine phosphatase (SHP2) is a non-receptor protein tyrosine phosphatase encoded by the Ptpn11 gene, which regulates cell growth, differentiation and apoptosis via modulating various signaling...


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