• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6215-6223
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• 2015

Tyrosine phosphorylation plays an important role in regulating human physiological and pathological processes. Functional stabilization of tyrosine phosphorylation largely contributes to the balanced, coordinated regulation of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Research has revealed PTPs play an important suppressive role in carcinogenesis and progression by reversing oncoprotein functions. Receptor-type protein tyrosine phosphatase O (PTPRO) as one member of the PTPs family has also been identified to have some roles in tumor development. Some reports have shown PTPRO over-expression in tumors can not only inhibit the frequency of tumor cell division and induce tumor cell death, but also suppress migration. However, the tumor-suppression mechanisms are very complex and understanding is incomplete, which in some degree blocks the further development of PTPRO. Hence, in order to resolve this problem, we here have summarized research findings to draw meaningful conclusions. We found tumor-suppression mechanisms of PTPRO to be diverse, such as controlling G0/G1 of the tumor cell proliferation cycle, inhibiting substrate phosphorylation, down-regulating transcription activators and other activities. In clinical anticancer efforts, expression level of PTPRO in tumors can not only serve as a biomarker to monitor the prognosis of patients, but act as an epigenetic biomarker for noninvasive diagnosis. In addition, the re-activation of PTPRO in tumor tissues, not only can induce tumor volume reduction, but also enhance the susceptibility to chemotherapy drugs. So, we can propose that these research findings of PTPRO will not only support new study ideas and directions for other tumor-suppressors, importantly, but also supply a theoretical basis for researching new molecular targeting agents in the future.

• Asian-Australasian Journal of Animal Sciences
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• v.19 no.7
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• pp.1033-1039
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• 2006

The metabolic response of Labeo rohita to thermal acclimation was assessed. Advanced fingerlings of L. rohita (average weight $31{\pm}1.4g$) were acclimated to 31, 33 and $36^{\circ}C$ compared with ambient temperatures ($26^{\circ}C$) for 30 days and different enzymes associated with stress response were estimated. Glycolytic enzyme-Lactate dehydrogenase, (LDH, E.C.1.1.1.27), TCA cycle enzyme-Malate dehydrogenase (MDH, E.C.1.1.1.37), Protein metabolizing enzymes-Aspartate amino transferase (AST, E.C.2.6.1.1) and Alanine amino transferase (ALT, E.C.2.6.1.2) of liver, gill and muscle, Gluconeogenic enzymes-Fructose 1,6 Bi phosphatase (FBPase, E.C. 3.1.3.11) and Glucose 6 phosphatase (G6Pase, E.C. 3.1.3.9) of liver and kidney were significantly (p<0.05) different with increasing acclimation temperatures. Heat Shock Protein-70 (HSP-70) was expressed in increasing intensity at 31, 33 and $36^{\circ}C$ but was not expressed at $26^{\circ}C$. Results suggest that higher acclimation temperatures enhance metabolism and L. rohita maintains homeostasis between $26-36^{\circ}C$ via an acclimation episode. Such adaptation appears to be facilitated by resorting to gluconeogenic and glycogenolytic pathways for energy mobilization and induction of HSPs.

• Journal of Applied Biological Chemistry
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• v.48 no.4
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• pp.183-186
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• 2005

Arabidopsis AHL gene encodes a 3'(2')-phosphoadenosine 5'-phosphate (PAP)-specific phosphatase that plays a role in the sulfate activation pathway. We complemented E. coli cysQ mutant defective in cysteine biosynthesis with the AHL gene. AHL cDNA was cloned into the prokaryotic expression vector pKK388-1 and transformed into the bacterial mutant. Since cysQ mutant is a leaky cysteine auxotroph only under aerobic conditions, the bacteria were grown in liquid media with vigorous shaking to provide more aeration. In cysteine-free medium, cysQ mutant and the mutant harboring empty vector did not grow well, whereas cells harboring AHL cDNA exhibited significantly improved growth with doubling time of approximately 3 h. cysQ is known to encode a 3'(2'),5'-diphosphonucleoside 3'(2')-phosphohydrolase (DPNPase). However, our data suggest that cysQ protein has PAP-specific phosphatase activity in addition to DPNPase activity. Microbial complementation procedure described in this paper is useful for structure-activity studies of PAP-specific phosphatases identified from microbes and plants.

• Journal of Trauma and Injury
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• v.26 no.3
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• pp.81-88
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• 2013

Purpose: Among patients with multiple traumatic fractures, a tendency to form more callus exists in groups with multiple fractures combined with traumatic brain injury. This retrospective study evaluated the hematologic factors that might be useful to predict callus formation by comparing serologic tests and clinical and radiologic results in two groups. Methods: From January 2000 to December 2010, patients with femur shaft fractures were divided in two groups: one without traumatic brain injury (control group: 32 cases), and the other with traumatic brain injury (study group: 44 cases). We evaluated routine serologic exams and the amount of callus formation during the follow-up period. Results: Only the alkaline phosphatase level was statistically different between the two groups, not the White blood cell count, C-reactive protein, total calcium, and lactate dehydrogenase level. The amount of callus formation on the antero-posterior radiograph at the last follow up period was 74.9% in the study group and 42.1% in the control group. Then lateral radiograph showed 73.2% callus formation rate in the study group and 31.8% in the control group. Conclusion: In routine serologic exams, the two groups had no significant differences, except for the alkaline phosphatase level. The group with traumatic brain injury had much more callus formation, but there was no reliable factor to predict callus formation on the routine serologic exam.

• Biomolecules & Therapeutics
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• v.31 no.2
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• pp.193-199
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• 2023

In this investigation, we made a study of the efficacy of luteolin (a flavonoid found in plants such as vegetables, herbs and fruits) on vascular contractibility and to elucidate the mechanism underlying the relaxation. Isometric contractions of denuded muscles were stored and combined with western blot analysis which was conducted to assess the phosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) and phosphorylation-dependent inhibitory protein for myosin phosphatase (CPI-17) and to examine the effect of luteolin on the RhoA/ROCK/CPI-17 pathway. Luteolin significantly alleviated phorbol ester-, fluoride- and thromboxane mimetic-elicited contractions regardless of endothelial nitric oxide synthesis, implying its direct effect on smooth muscle. It also significantly alleviated the fluoride-elicited elevation in pCPI-17 and pMYPT1 levels and phorbol 12,13-dibutyrate-elicited increase in pERK1/2 level, suggesting depression of ROCK and PKC/MEK activity and ensuing phosphorylation of MYPT1, CPI-17 and ERK1/2. Taken together, these results suggest that luteolin-elicited relaxation includes myosin phosphatase reactivation and calcium desensitization, which seems to be arbitrated by CPI-17 dephosphorylation via ROCK/PKC inhibition.

• BMB Reports
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• v.56 no.9
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• pp.508-513
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• 2023

The phytochemical quercetin has gained attention for its anti-inflammatory and anti-tumorigenic properties in various types of cancer. Tumorigenesis involves the aberrant regulation of kinase/phosphatase, highlighting the importance of maintaining homeostasis. Dual Specificity Phosphatase (DUSP) plays a crucial role in controlling the phosphorylation of ERK. The current study aimed to clone the DUSP5 promoter, and investigate its transcriptional activity in the presence of quercetin. The results revealed that quercetin-induced DUSP5 expression is associated with the serum response factor (SRF) binding site located in the DUSP5 promoter. The deletion of this site abolished the luciferase activity induced by quercetin, indicating its vital role in quercetin-induced DUSP5 expression. SRF protein is a transcription factor that potentially contributes to quercetin-induced DUSP5 expression at the transcriptional level. Additionally, quercetin enhanced SRF binding activity without changing its expression. These findings provide evidence of how quercetin affects anti-cancer activity in colorectal tumorigenesis by inducing SRF transcription factor activity, thereby increasing DUSP5 expression at the transcriptional level. This study highlights the importance of investigating the molecular mechanisms underlying the anti-cancer properties of quercetin, and suggests its potential use in cancer therapy.

• Biomolecules & Therapeutics
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• v.30 no.2
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• pp.145-150
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• 2022

In this study, we investigated the influence of galangin on vascular contractibility and to determine the mechanism underlying the relaxation. Isometric contractions of denuded aortic muscles were recorded and combined with western blot analysis which was performed to measure the phosphorylation of phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17) and myosin phosphatase targeting subunit 1 (MYPT1) and to evaluate the effect of galangin on the RhoA/ROCK/CPI-17 pathway. Galangin significantly inhibited phorbol ester-, fluoride- and thromboxane mimetic-induced vasoconstrictions regardless of endothelial nitric oxide synthesis, suggesting its direct effect on vascular smooth muscle. Galangin significantly inhibited the fluoride-dependent increase in pMYPT1 and pCPI-17 levels and phorbol 12,13-dibutyrate-dependent increase in pERK1/2 level, suggesting repression of ROCK and MEK activity and subsequent phosphorylation of MYPT1, CPI-17 and ERK1/2. Taken together, these results suggest that galangin-induced relaxation involves myosin phosphatase reactivation and calcium desensitization, which appears to be mediated by CPI-17 dephosphorylation via not PKC but ROCK inactivation.

• Biomolecules & Therapeutics
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• v.32 no.3
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• pp.361-367
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• 2024

In this study, we investigated the efficacy of kaempferol (a flavonoid found in plants and plant-derived foods such as kale, beans, tea, spinach and broccoli) on vascular contractibility and aimed to clarify the detailed mechanism underlying the relaxation. Isometric contractions of divested muscles were stored and linked with western blot analysis which was carried out to estimate the phosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) and phosphorylation-dependent inhibitory protein for myosin phosphatase (CPI-17) and to estimate the effect of kaempferol on the RhoA/ROCK/CPI-17 pathway. Kaempferol conspicuously impeded phorbol ester-, fluoride- and a thromboxane mimetic-derived contractions regardless of endothelial nitric oxide synthesis, indicating its direct effect on smooth muscles. It also conspicuously impeded the fluoride-derived elevation in phospho-MYPT1 rather than phospho-CPI-17 levels and phorbol 12,13-dibutyrate-derived increase in phospho-CPI-17 and phospho-ERK1/2 levels, suggesting the depression of PKC and MEK activities and subsequent phosphorylation of CPI-17 and ERK1/2. Taken together, these outcomes suggest that kaempferol-derived relaxation incorporates myosin phosphatase retrieval and calcium desensitization, which appear to be modulated by CPI-17 dephosphorylation mainly through PKC inactivation.

• BMB Reports
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• v.45 no.12
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• pp.693-699
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• 2012

Together with protein tyrosine kinases (PTKs), protein tyrosine phosphatases (PTPs) serve as hallmarks in cellular signal transduction by controlling the reversible phosphorylation of their substrates. The human genome is estimated to encode more than 100 PTPs, which can be divided into eleven sub-groups according to their structural and functional characteristics. All the crystal structures of catalytic domains of sub-groups have been elucidated, enabling us to understand their precise catalytic mechanism and to compare their structures across all sub-groups. In this review, I describe the structure and mechanism of catalytic domains of PTPs in the structural context.

• Molecules and Cells
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• v.39 no.9
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• pp.654-662
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• 2016

Almost all eukaryotic proteins are subject to post-translational modifications during mitosis and cell cycle, and in particular, reversible phosphorylation being a key event. The recent use of high-throughput experimental analyses has revealed that more than 70% of all eukaryotic proteins are regulated by phosphorylation; however, the mechanism of dephosphorylation, counteracting phosphorylation, is relatively unknown. Recent discoveries have shown that many of the protein phosphatases are involved in the temporal and spatial control of mitotic events, such as mitotic entry, mitotic spindle assembly, chromosome architecture changes and cohesion, and mitotic exit. This implies that certain phosphatases are tightly regulated for timely dephosphorylation of key mitotic phosphoproteins and are essential for control of various mitotic processes. This review describes the physiological and pathological roles of mitotic phosphatases, as well as the versatile role of various protein phosphatases in several mitotic events.