β-Arrestin2 directly or through GRK2 inhibits PKCβII activation in a ubiquitination-dependent manner

Zhang, Xiaohan,Zheng, Mei,Sun, Ningning,Kim, Kyeong-Man Elsevier 2018 Biochimica et biophysica acta, Molecular cell rese Vol.1865 No.1

<P><B>Abstract</B></P> <P>The GRK/β-arrestin and PKC/PKA mediate the homologous and heterologous regulation of G protein-coupled receptors (GPCRs), respectively. Interaction between the two pathways is one of the most important issues in understanding the regulation of GPCRs. The present study investigated the regulatory effect of GRK2 and β-arrestins on PKC activation. The roles of GRK2 and β-arrestins in the functional regulation of PKC were assessed by determining their influence on PKC autophosphorylation and intracellular translocation. Radioligand binding assay was utilized to characterize intracellular trafficking of dopamine D<SUB>2</SUB>R, D<SUB>3</SUB>R, and β<SUB>2</SUB> adrenergic receptor (β<SUB>2</SUB>AR). The subdomains involved in the mutual interactions among GRK2, β-arrestin2, and PKCβII were determined by in vitro binding assay. Various point mutants of key regulatory players were combined with knockdown cells of GRK2, β-arrestins, and Mdm2 to functionally correlate the biochemical changes with functional outcomes. GRK2 and β-arrestin2 mutually inhibited the PKCβII autophosphorylation, a hallmark of PKCβII activation. β-Arrestin2 ubiquitination was required for the inhibitory activities of GRK2 as well as β-arrestin2. Furthermore, GRK2 facilitated β-arrestin2 ubiquitination, thus to enhance the inhibitory actions of β-arrestin2 on PKCβII activity. Aforementioned processes were also involved in the GRK2/β-arrestin2-mediated inhibition of the D<SUB>2</SUB>R, D<SUB>3</SUB>R, and β<SUB>2</SUB>AR endocytosis. The present study provides new insights into the intricate interactions between the homologous and heterologous GPCR regulation pathways. In addition, a novel regulatory role of GRK2 was proposed for the ubiquitination of β-arrestin in the context of the PKC-mediated heterologous regulation of GPCRs.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A novel regulatory mechanism for the GPCR regulation is proposed. </LI> <LI> The mechanism relies on GRK2/β-arrestin2-mediated inhibition of PKC. </LI> <LI> The ubiquitination of β-arrestin2 is required for the inhibition of PKC. </LI> <LI> GRK2 potentiates the ubiquitination of β-arrestin2. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Camouflage color

Zhang Xiaohan 한국콘텐츠학회 2022 ICCC International Digital Design Invitation Exhib Vol.2022 No.07

Multifactorial Regulation of G Protein-Coupled Receptor Endocytosis

Zhang, Xiaohan,Kim, Kyeong-Man The Korean Society of Applied Pharmacology 2017 Biomolecules & Therapeutics(구 응용약물학회지) Vol.25 No.1

Endocytosis is a process by which cells absorb extracellular materials via the inward budding of vesicles formed from the plasma membrane. Receptor-mediated endocytosis is a highly selective process where receptors with specific binding sites for extracellular molecules internalize via vesicles. G protein-coupled receptors (GPCRs) are the largest single family of plasma-membrane receptors with more than 1000 family members. But the molecular mechanisms involved in the regulation of GPCRs are believed to be highly conserved. For example, receptor phosphorylation in collaboration with ${\beta}$-arrestins plays major roles in desensitization and endocytosis of most GPCRs. Nevertheless, a number of subsequent studies showed that GPCR regulation, such as that by endocytosis, occurs through various pathways with a multitude of cellular components and processes. This review focused on i) functional interactions between homologous and heterologous pathways, ii) methodologies applied for determining receptor endocytosis, iii) experimental tools to determine specific endocytic routes, iv) roles of small guanosine triphosphate-binding proteins in GPCR endocytosis, and v) role of post-translational modification of the receptors in endocytosis.

Multifactorial Regulation of G Protein-Coupled Receptor Endocytosis

( Xiaohan Zhang ),( Kyeong-man Kim ) 한국응용약물학회 2017 Biomolecules & Therapeutics(구 응용약물학회지) Vol.25 No.1

Endocytosis is a process by which cells absorb extracellular materials via the inward budding of vesicles formed from the plasma membrane. Receptor-mediated endocytosis is a highly selective process where receptors with specific binding sites for extracel-lular molecules internalize via vesicles. G protein-coupled receptors (GPCRs) are the largest single family of plasma-membrane receptors with more than 1000 family members. But the molecular mechanisms involved in the regulation of GPCRs are believed to be highly conserved. For example, receptor phosphorylation in collaboration with β-arrestins plays major roles in desensitization and endocytosis of most GPCRs. Nevertheless, a number of subsequent studies showed that GPCR regulation, such as that by endocytosis, occurs through various pathways with a multitude of cellular components and processes. This review focused on i) functional interactions between homologous and heterologous pathways, ii) methodologies applied for determining receptor en-docytosis, iii) experimental tools to determine specific endocytic routes, iv) roles of small guanosine triphosphate-binding proteins in GPCR endocytosis, and v) role of post-translational modification of the receptors in endocytosis.

Is Huawei a Leverage of the US-China Trade War? A Critical Reflection on the Huawei Case

Xiaohan Zhang 이준국제법연구원 2019 China and WTO Review Vol.5 No.1

On January 28, 2019, the US Department of Justice announced criminal charges against Huawei. A pair of indictments accusing Huawei of violating the US sanctions as well as stealing trade secrets was unsealed in two separate cases. In fact, as a technology-intensive enterprise, Huawei has always been under close scrutiny from the US government for ‘national security’ concerns, and both the criminal allegations have existed for years. The Chinese side questioned the American motives, accusing that the US is actually using law enforcement as one tool among many to achieve its policy objectives in the Huawei case. The article presents the Chinese side of the case as well as the grounds for its position.

Roles of Dopamine D₂ Receptor Subregions in Interactions with β-Arrestin2

Zhang, Xiaohan,Choi, Bo-Gil,Kim, Kyeong-Man The Korean Society of Applied Pharmacology 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.5

${\beta}$-Arrestins are one of the protein families that interact with G protein-coupled receptors (GPCRs). The roles of ${\beta}$-arrestins are multifaceted, as they mediate different processes including receptor desensitization, endocytosis, and G protein-independent signaling. Thus, determining the GPCR regions involved in the interactions with ${\beta}$-arrestins would be a preliminary step in understanding the molecular mechanisms involved in the selective direction of each function. In the current study, we determined the roles of the N-terminus, intracellular loops, and C-terminal tail of a representative GPCR in the interaction with ${\beta}$-arrestin2. For this, we employed dopamine $D_2$ and $D_3$ receptors ($D_2R$ and $D_3R$, respectively), since they display distinct agonist-induced interactions with ${\beta}$-arrestins. Our results showed that the second and third intracellular loops of $D_2R$ are involved in the agonist-induced translocation of ${\beta}$-arrestins toward plasma membranes. In contrast, the N- and C-termini of $D_2R$ exerted negative effects on the basal interaction with ${\beta}$-arrestins.

Roles of Dopamine D₂ Receptor Subregions in Interactions with β-Arrestin2

( Xiaohan Zhang ),( Bo-gil Choi ),( Kyeong-man Kim ) 한국응용약물학회 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.5

β -Arrestins are one of the protein families that interact with G protein-coupled receptors (GPCRs). The roles of β -arrestins are multifaceted, as they mediate different processes including receptor desensitization, endocytosis, and G protein-independent signaling. Thus, determining the GPCR regions involved in the interactions with β -arrestins would be a preliminary step in understanding the molecular mechanisms involved in the selective direction of each function. In the current study, we determined the roles of the N-terminus, intracellular loops, and C-terminal tail of a representative GPCR in the interaction with β -arrestin2. For this, we employed dopamine D₂ and D₃ receptors (D₂ R and D₃ R, respectively), since they display distinct agonist-induced interactions with β -arrestins. Our results showed that the second and third intracellular loops of D₂R are involved in the agonist-induced translocation of β -arrestins toward plasma membranes. In contrast, the N- and C-termini of D₂R exerted negative effects on the basal interaction with β -arrestins.

Experimental Study on Thermal Catalytic Degradation of SF6 Waste Gas by Metal Phosphate

Zhang Xiaoxing,Li Xiaohan,Wang Yi,Meng Fei,Zou Yi,Tian Shuangshuang,Cui Zhaolun 대한전기학회 2023 Journal of Electrical Engineering & Technology Vol.18 No.2

In recent years, SF6 has been widely used in the electrical industry. The amount of SF6 waste gas produced by the corresponding gas insulated equipment is increasing year by year. However, SF6 has high global warming potential and long atmospheric life. Proper treatment of SF6 waste gas is particularly important for environmental protection. Thermal degradation can effectively eliminate the greenhouse effect caused by direct emission of SF6. In this paper, AlPO4, Zr3(PO4)4 and CePO4 were used as catalysts to degrade SF6/air mixture gas (The concentration of SF6 is 15%) at 800 °C. The concentration of SF6 gas was detected by gas chromatography (GC), and the gas decomposition products of SF6 were detected by gas chromatography mass spectrometry (GCMS) and fourier transform infrared spectroscopy (FTIR). The surface morphology and composition of the catalyst were analyzed by scanning electron microscope (SEM) and X-ray photoelectron spectroscopy (XPS). The results show that the three kinds of metal phosphates can promote the decomposition of SF6 gas, among which CePO4 had the best catalytic degradation effect, and the degradation rate of SF6 reached 84.7% in 12 h. The main products of SF6 gas thermal catalytic degradation include SF4, S2F10, SO2F2, SOF2, SiF4 and SO2 gas, etc. SEM scanning image shows that there were some objects adsorbed on the surface of CePO4 catalyst after the experiment. XPS spectra showed that Si and F elements were added to the catalyst. According to the binding energy, SiF4 was adsorbed on the catalyst. After the experiment, CeF3 was produced by CePO4 catalyst. Different catalysts have their own selectivity to the decomposition products of SF6, which is convenient for the treatment of products, and it is of great significance to eliminate the greenhouse effect caused by the waste gas of SF6.

Elasto-plastic time history analysis of a 117-story high structure

Xiaohan Wu,Yimiao Li,Yunlei Zhang 사단법인 한국계산역학회 2017 Computers and Concrete, An International Journal Vol.19 No.1

In Chinese Design Codes, for super high-rise buildings with complex structural distribution, which are regarded as code-exceeding buildings, elasto-plastic time history analysis is needed to validate the requirement of “no collapse under rare earthquake”. In this paper, a 117-story super high-rise building is discussed. It has a height of 597 m and a height-width ratio of 9.5, which have both exceeded the limitations stipulated by the Chinese Design Codes. Mega columns adopted in this structure have cross section area of about 45 m2 at the bottom, which is infrequent in practical projects. NosaCAD and Perform-3D, both widely used in nonlinear analyses, were chosen in this study, with which two model were established and analyzed, respectively. Elasto-plastic time history analysis was conducted to look into its seismic behavior, emphasizing on the stress state and deformation abilities under intensive seismic excitation.From the comparisons on the results under rare earthquake obtained from NosaCAD and Perform-3D, the overall responses such as roof displacement, inter story drift, base shear and damage pattern of the whole structure from each software show agreement to an extent. Besides, the deformation of the structure is below the limitation of the Chinese Codes, the time sequence and distribution of damages on core tubes are reasonable, and can dissipate certain inputted energy, which indicates that the structure can meet the requirement of “no collapse under rare earthquake”.

miRNA Pattern Discovery from Sequence Alignment

Xiaohan Sun,Junying Zhang 한국정보처리학회 2017 Journal of information processing systems Vol.13 No.6

MiRNA is a biological short sequence, which plays a crucial role in almost all important biological process. MiRNA patterns are common sequence segments of multiple mature miRNA sequences, and they are ofsignificance in identifying miRNAs due to the functional implication in miRNA patterns. In the proposedapproach, the primary miRNA patterns are produced from sequence alignment, and they are then cut intoshort segment miRNA patterns. From the segment miRNA patterns, the candidate miRNA patterns areselected based on estimated probability, and from which, the potential miRNA patterns are further selectedaccording to the classification performance between authentic and artificial miRNA sequences. Threeparameters are suggested that bi-nucleotides are employed to compute the estimated probability of segmentmiRNA patterns, and top 1% segment miRNA patterns of length four in the order of estimated probabilitiesare selected as potential miRNA patterns.