EphA Receptors Form a Complex with Caspase-8 to Induce Apoptotic Cell Death

Lee, Haeryung,Park, Sunjung,Kang, Young-Sook,Park, Soochul Korean Society for Molecular and Cellular Biology 2015 Molecules and cells Vol.38 No.4

EphA7 has been implicated in the regulation of apoptotic cell death in neural epithelial cells. In this report, we provide evidence that EphA7 interacts with caspase-8 to induce apoptotic cell signaling. First, a pull-down assay using biotinylated ephrinA5-Fc showed that EphA7 co-precipitated with wild type caspase-8 or catalytically inactive caspase-8 mutant. Second, co-transfection of EphA7 with caspase-8 significantly increased the number of cleaved caspase-3 positive apoptotic cells under an experimental condition where transfection of EphA7 or caspase-8 alone did not affect cell viability or apoptosis. EphA4 also had a causative role in inducing apoptotic cell death with caspase-8, whereas EphA8 did not. Third, caspase-8 catalytic activity was essential for the apoptotic signaling cascade, whereas tyrosine kinase activity of the EphA4 receptor was not. Interestingly, we found that kinase-inactive EphA4 was well co-localized at the plasma membrane with catalytically inactive caspase-8, suggesting that an interaction between these mutant proteins was more stable. Finally, we observed that the extracellular region of the EphA7 receptor was critical for interacting with caspase-8, whereas the cytoplasmic region of EphA7 was not. Therefore, we propose that Eph receptors physically associate with a transmembrane protein to form an apoptotic signaling complex and that this unidentified receptor-like protein acts as a biochemical linker between the Eph receptor and caspase-8.

‘학생선수’ 개념의 의미 변천과 교육적 함의 도출

이해령(Haeryung Lee),류태호(Taeho Yu) 한국스포츠교육학회 2021 한국스포츠교육학회지 Vol.28 No.2

본 연구는 학생선수 개념의 의미가 시간의 흐름에 따라 변화할 것이란 전제를 바탕으로, 학생선수 개념이 시대별로 어떠한 의미의 변화를 겪으면서 담론이 되었는지 분석하고, 관련하여 스포츠교육계에 던질 새로운 교육적 함의를 제공하는 목적으로 수행되었다. 이를 위해 1970년대부터 2020년 사이에 국내에서 발간된 정책 보고서 및 문서 90여 편, 언론자료 약 400여 개가 수집되었고, 담론분석론에 기대어 작성한 분석틀을 토대로 학생선수 개념의 의미와 담론화를 분석하였다. 분석 결과, 1970-80년대에는 학습하지 않는 학교대표 운동선수, 1990년대에는 운동으로 대학 가는 학교운동부, 2000년대 공부하는 학생선수라는 의미가 덧붙여진 후, 2010년대에는 정책적 인권 보호 대상의 의미가 포함되었다. 즉, 개념이 지닌 의미는 시대의 흐름에 따라 누적되어 확장되었다. 이러한 의미의 변천을 통해 파악된 학생선수 개념은 운동(권), 학습권, 인권으로 담론화되었고, 이 담론들은 소멸 또는 대체된 것이 아니라 시기나 문제 상황에 따라 그 영향력을 달리하며 공존하고 있었다. 연구결과를 토대로 도출한 세 가지 교육적 함의는 첫째, 학생선수가 해야 할 공부와 역량에 대한 논의, 둘째, 관련 문제 해결에 대한 교육의 가능성 재고, 셋째, 학생선수 담론 확장의 필요성이다. 이는 학생선수와 관련된 새로운 논의 지점이 될 수 있음을 시사한다. The purpose of this study is to explore the concept of ‘student-athlete’ emerged and the ways in which its meanings have change-down. Specifically, this study traces in detail how the concept of student-athlete has become a discourse, how the meaning of the concept has changed over time. To achieve this purpose, this study collected 90 policy reports and documents, 399 media materials, and records of policy changes published between the year 1970 and February 2020. Furthermore, the inquiry drew on the theory of discourse analysis and the materials was investigated and interpreted through the analytical frameworks. As a result, different meaning of the term student-athlete has accumulated and expanded from the 1970s-80s to 2010s; in the 1970s-80s, it meant athletes who represent school but do not study; in the 1990s it meant students playing for school athletics and who enter college with athletic performances; in the 2000s it meant student-athletes who both study and exercise; and in the 2010s it meant student-athletes whose human rights needed to be protected. And three discourses was the right to exercise, the right to learn and human rights. At the end of these results, there are three conclusions of this study, summarized from a pedagogical point of view. The first is the discussion of competence and definition of studying. The second is the reconsideration of the function of education. The third is an expansion of discourses of student-athlete.

The SAM Domains of Anks Family Proteins Are Critically Involved in Modulating the Degradation of EphA Receptors

Kim, Jieun;Lee, Haeryung;Kim, Yujin;Yoo, Sooyeon;Park, Eunjeong;Park, Soochul 숙명여자대학교 여성건강연구소 2011 여성과 건강 Vol.6 No.2

We recently reported that the phosphotyrosine-binding (PTB) domain of Anks family proteins binds to EphA8,thereby positively regulating EphA8-mediated signaling pathways. In the current study, we identified a potential role for the SAM domains of Anks family proteins in EphA signaling. We found that SAM domains of Anks family proteins directly bind to ubiquitin, suggesting that Anks proteins regulate the degradation of ubiquitinated EphA receptors. Consistent with the role of Cbl ubiquitin ligases in the degradation of Eph receptors, our results revealed that the ubiquitin ligase c-Cbl induced the ubiquilinaiion and degradation of EphA8 upon ligand binding. Ubiquitinated EphA8 also bound to the SAM domains of Odin, a member of the Anks family proteins. More importantly, the overexpression of wild-type Odin protected EphA8 and EphA2 from undergoing degradation following ligand stimulation and promoted EphA-mediated inhibition of cell migration. In contrast,a SAM domain deletion mutant of Odin strongly impaired the function of endogenous Odin, suggesting that the mutant functions in a dominant-negative manner. An analysis of Odin-deficient primary embryonic fibroblasts indicated that Odin levels play a critical role in regulating the stability of EphA2 in response to ligand stimulation. Taken together,our studies suggest that the SAM domains of Anks family proteins play a pivotal role in enhancing the stability of EphA receptors by modulating the ubiquitination process.

치과의사와 치과위생사의 번아웃(burnout) 현황과 관련 요인

박유이 ( Yuyi Park ),이지현 ( Jihyun Lee ),배소휘 ( Sohwi Bae ),이기찬 ( Kichan Lee ),이상혁 ( Sangheuk Lee ),장수진 ( Soojin Jang ),허해령 ( Haeryung Hur ),박영훈 ( Younghoon Park ) 대한예방치과·구강보건학회 2019 大韓口腔保健學會誌 Vol.43 No.2

Objectives: Dentists and dental hygienists undergo high levels of stress due to various factors and the burnout of health-care personnel is very important in the context of personal and social problems. Therefore, empirical research reflecting the social, cultural, and special circumstances of the medical environment is necessary. Here, we explore the causes and outcomes of burnout in dentists and dental hygienists and present ways to prevent burnout. Methods: A cross-sectional research design was used to measure burnout of 141 dentists and 61 dental hygienists. A structured questionnaire containing the Maslach Burnout Inventory (MBI) was administered from May to June, 2018. Data were analyzed using SPSS 25.0, descriptive statistics, t-test, Mann-Whitney test, Kruskall-Wallis test, and multiple regression analysis. Results: Each participant’s MBI was measured in three aspects (emotional exhaustion, depersonalization, and personal accomplishment). The MBI scores of dentists with regards to their emotional exhaustion, depersonalization, and personal accomplishment were 24.8%, 34%, and 48.2%, respectively. Alternatively the scores of dental hygienists were 45.9%, 44.3% and 52.5%, respectively, for the same parameters. While the factors affecting the burnout of dentists and dental hygienists were different, it had a negative impact on the professional performance of both. Conclusions: According to the results of this study, Korean dentists and dental hygienists experience high levels of work-related burnouts. This can have adverse impacts on their personal health and that of their patients. Therefore, stress management is necessary in dentists and dental hygienists.

Bollnow의 “교육적 분위기” 개념을 통해 본 어린이-교사 관계론

이현주(Lee HyunJoo),유혜령(Yeu HaeRyung) 한국열린유아교육학회 2004 열린유아교육연구 Vol.8 No.4

이 연구에서는 과학적 교육론이 지배적인 현대에 교육적 상황의 정서적 측면이나 분위기 요소의 현상학적 중요성을 주장한 독일의 실존교육론자 Otto F. Bollnow의 ‘교육적 분위기’ 개념을 소개하고, 이를 통해 어떠한 형태의 어린이와 교사간 관계가 강조 되고 있는지 살펴본다. 그는 어린이의 입장에서 볼 때 교육적인 분위기는 안정과 즐거움이 깃든 것이어야 하고, 어린이의 자발적인 감사와 순종의 본성을 북돋아줄 수 있는 특성을 지니고 있어야 하며, 교사의 입장에서는 어린이에 대한 신뢰, 사랑과 인내의 덕목이 교육적 분위기의 핵심 요소가 된다고 하였다. 이 같은 분위기 속에서 맺어지는 어린이-교사 관계는 ’근원적 마음씀’의 관계, 지평융합적 나-너의 관계 만남의 관계, 기다림과 희망의 관계로 해석된다. 교육 현장의 분위기의 현상적 특성과 관계맺음의 성격은 교육이 근원적으로 인간관계에 기초하며 그 관계기 엮어내는 각각의 구체적인 맥락과 분리될 수 없는 것임을 알려 준다. It is attempted in this study to question what might be the desirable relationship between child and teacher in the Otto F. Bollnow's notion of "pedagogical atmosphere." This is to reconceptualize the genuine nature of child-teacher relationship going beyond the scientific notion of child-teacher relationship, that is hierarchical, uni-directional, and power-laden. The Bollnow's notion of "pedagogical atmosphere" is the foremost example of his phenomenological analyses on educational reality, and thereby this study focuses on the anthropological and phenomenological understanding of the child-teacher relationship. In his analyses on pedagogical atmosphere, Bollnow emphasizes, from child's perspective, the voluntary gratitude and obedience as the child's intrinsic natures, and suggests that pedagogical atmosphere for child should be filled with the feeling of security and joy. From teacher's perspective, he stresses the trust in child's being and capability and the virtues of love and patience as the crucial components of being a teacher. In such atmosphere child and teacher get into the process of mutual "Bildung," i.e. the relationship of the fundamental care(Sorge) of and waiting for each other's being, the I-Thou relationship leading to a true "encounter" and to the fusion of different horizons of each other. This relationship would be truely pedagogical as it relates a child to a teacher and vice versa, within which they come to belong to mutual hope for each other.

Proper closure of the optic fissure requires ephrin A5-EphB2-JNK signaling

Noh, Hyuna,Lee, Haeryung,Park, Eunjeong,Park, Soochul The Company of Biologists Limited 2016 Development (Cambridge) Vol.143 No.3

<P>The development of complex organs such as the eye requires a delicate and coordinated balance of cell division and cell death. Although apoptosis is prevalent in the proximoventral optic cup, the precise role it plays in eye development needs to be investigated further. In this study, we show that reduced apoptosis in the proximoventral optic cup prevents closure of the optic fissure. We also show that expression of ephrin A5 (Efna5) partially overlaps with Eph receptor B2 (Ephb2) expression in the proximoventral optic cup and that binding of EphB2 to ephrin A5 induces a sustained activation of JNK. This prolonged JNK signal promotes apoptosis and prevents cell proliferation. Thus, we propose that the unique cross-subclass interaction of EphB2 with ephrin A5 has evolved to function upstream of JNK signaling for the purpose of maintaining an adequate pool of progenitor cells to ensure proper closure of the optic fissure.</P>

Expanding association between BICD2 variants and brain malformations and associated lissencephaly

Jaeso Cho,Haeryung Kim,Seoungbok Lee,Jihoon G. Yoon,HyeJin Kim,Min-Hye Kim,Seoyun Jang,Woo Joong Kim,Soo Yeon Kim,Jong-Hee Chae 대한소아청소년과학회 2024 Clinical and Experimental Pediatrics (CEP) Vol.67 No.1

Deup1 expression interferes with multiciliated differentiation

신미람,Jiyeon Lee,Haeryung Lee,Vijay Kumar,김재봉,박수철 한국분자세포생물학회 2023 Molecules and cells Vol.46 No.12

A recent study revealed that the loss of Deup1 expression does not affect either centriole amplification or multicilia formation. Therefore, the deuterosome per se is not a platform for amplification of centrioles. In this study, we examine whether gain-of-function of Deup1 affects the development of multiciliated ependymal cells. Our time-lapse study reveals that deuterosomes with an average diameter of 300 nm have two different fates during ependymal differentiation. In the first instance, deuterosomes are scattered and gradually disappear as cells become multiciliated. In the second instance, deuterosomes self-organize into a larger aggregate, called a deuterosome cluster (DC). Unlike scattered deuterosomes, DCs possess centriole components primarily within their large structure. A characteristic of DC-containing cells is that they tend to become primary ciliated rather than multiciliated. Our in utero electroporation study shows that DCs in ependymal tissue are mostly observed at early postnatal stages, but are scarce at late postnatal stages, suggesting the presence of DC antagonists within the differentiating cells. Importantly, from our bead flow assay, ectopic expression of Deup1 significantly impairs cerebrospinal fluid flow. Furthermore, we show that expression of mouse Deup1 in Xenopus embryos has an inhibitory effect on differentiation of multiciliated cells in the epidermis. Taken together, we conclude that the DC formation of Deup1 in multiciliated cells inhibits production of multiple centrioles.

In Vivo Expression of the PTB-deleted Odin Mutant Results in Hydrocephalus

Park, Sunjung,Lee, Haeryung,Park, Soochul Korean Society for Molecular and Cellular Biology 2015 Molecules and cells Vol.38 No.5

Odin has been implicated in the downstream signaling pathway of receptor tyrosine kinases, such as the epidermal growth factor and Eph receptors. However, the physiologically relevant function of Odin needs to be further determined. In this study, we used Odin heterozygous mice to analyze the Odin expression pattern; the targeted allele contained a ${\beta}$-geo gene trap vector inserted into the 14t intron of the Odin gene. Interestingly, we found that Odin was exclusively expressed in ependymal cells along the brain ventricles. In particular, Odin was highly expressed in the subcommissural organ, a small ependymal glandular tissue. However, we did not observe any morphological abnormalities in the brain ventricles or ependymal cells of Odin null-mutant mice. We also generated BAC transgenic mice that expressed the PTB-deleted Odin (dPTB) after a floxed GFP-STOP cassette was excised by tissue-specific Cre expression. Strikingly, Odin-dPTB expression played a causative role in the development of the hydrocephalic phenotype, primarily in the midbrain. In addition, Odin-dPTB expression disrupted proper development of the subcommissural organ and interfered with ependymal cell maturation in the cerebral aqueduct. Taken together, our findings strongly suggest that Odin plays a role in the differentiation of ependymal cells during early postnatal brain development.

The SAM Domains of Anks Family Proteins Are Critically Involved in Modulating the Degradation of EphA Receptors

Kim, Jieun,Lee, Haeryung,Kim, Yujin,Yoo, Sooyeon,Park, Eunjeong,Park, Soochul American Society for Microbiology 2010 Molecular and cellular biology Vol.30 No.7

<B>ABSTRACT</B><P>We recently reported that the phosphotyrosine-binding (PTB) domain of Anks family proteins binds to EphA8, thereby positively regulating EphA8-mediated signaling pathways. In the current study, we identified a potential role for the SAM domains of Anks family proteins in EphA signaling. We found that SAM domains of Anks family proteins directly bind to ubiquitin, suggesting that Anks proteins regulate the degradation of ubiquitinated EphA receptors. Consistent with the role of Cbl ubiquitin ligases in the degradation of Eph receptors, our results revealed that the ubiquitin ligase c-Cbl induced the ubiquitination and degradation of EphA8 upon ligand binding. Ubiquitinated EphA8 also bound to the SAM domains of Odin, a member of the Anks family proteins. More importantly, the overexpression of wild-type Odin protected EphA8 and EphA2 from undergoing degradation following ligand stimulation and promoted EphA-mediated inhibition of cell migration. In contrast, a SAM domain deletion mutant of Odin strongly impaired the function of endogenous Odin, suggesting that the mutant functions in a dominant-negative manner. An analysis of Odin-deficient primary embryonic fibroblasts indicated that Odin levels play a critical role in regulating the stability of EphA2 in response to ligand stimulation. Taken together, our studies suggest that the SAM domains of Anks family proteins play a pivotal role in enhancing the stability of EphA receptors by modulating the ubiquitination process.</P>