• Molecules and Cells
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• 제38권10호
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• pp.829-835
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• 2015

It has been suggested that AUXIN BINDING PROTEIN 1 (ABP1) functions as an apoplastic auxin receptor, and is known to be involved in the post-transcriptional process, and largely independent of the already well-known SKP-cullin-F-box-transport inhibitor response (TIR1) /auxin signaling F-box (AFB) ($SCF^{TIR1/AFB}$) pathway. In the past 10 years, several key components downstream of ABP1 have been reported. After perceiving the auxin signal, ABP1 interacts, directly or indirectly, with plasma membrane (PM)-localized transmembrane proteins, transmembrane kinase (TMK) or SPIKE1 (SPK1), or other unidentified proteins, which transfer the signal into the cell to the Rho of plants (ROP). ROPs interact with their effectors, such as the ROP interactive CRIB motif-containing protein (RIC), to regulate the endocytosis/exocytosis of the auxin efflux carrier PIN-FORMED (PIN) proteins to mediate polar auxin transport across the PM. Additionally, ABP1 is a negative regulator of the traditional $SCF^{TIR1/AFB}$ auxin signaling pathway. However, Gao et al. (2015) very recently reported that ABP1 is not a key component in auxin signaling, and the famous abp1-1 and abp1-5 mutant Arabidopsis lines are being called into question because of possible additional mutantion sites, making it necessary to reevaluate ABP1. In this review, we will provide a brief overview of the history of ABP1 research.

• Journal of Ginseng Research
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• 제47권1호
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• pp.89-96
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• 2023

Background and aim: Panax ginseng, a key herbal medicine of replenishing Qi and tonifying Spleen, is widely used in the treatment of gastrointestinal diseases in East Asia. In this study, we aim to investigate the potential effects and mechanisms of polysaccharides from P. ginseng (PGP) on intestinal mucosal restitution which is one of the crucial repair modalities during the recovery of mucosal injury controlled by the Ca²⁺ signaling. Methods: Rat model of intestinal mucosal injury was induced by indomethacin. The fractional cell migration was carried out by immunohistochemistry staining with BrdU. The morphological observations on intestinal mucosal injury were also performed. Intestinal epithelial cell (IEC-6) migration in vitro was conducted by scratch method. Western-blot was adopted to determine the expressions of PLC-𝛾1, Rac1, TRPC1, RhoA and Cav-1. Immunoprecipitation was used to evaluate the levels of Rac1/PLC-𝛾1, RhoA/TRPC1 and Cav-1/TRPC1. Results: The results showed that PGP effectively reduced the assessment of intestinal mucosal injury, reversed the inhibition of epithelial cell migration induced by Indomethacin, and increased the level of Ca²⁺ in intestinal mucosa in vivo. Moreover, PGP dramatically promoted IEC-6 cell migration, the expression of Ca²⁺ regulators (PLC-𝛾1, Rac1, TRPC1, Cav-1 and RhoA) as well as protein complexes (Rac1/PLC-𝛾1, Cav-1/TRPC1 and RhoA/TRPC1) in vitro. Conclusion: PGP increases the Ca²⁺ content in intestinal mucosa partly through controlling the regulators of Ca²⁺ mobilization, subsequently promotes intestinal epithelial cell migration, and then prevents intestinal mucosal injury induced by indomethacin.

• 생명과학회지
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• 제13권6호
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• pp.903-910
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• 2003

Phosphipase D(PLD)는 호중구의 활성에서 중요한 신호전달 인자로 작용한다. 본 연구에서는 호중구에서 PLD의 활성화에 대한 nitric oxide(NO)와 cGMP의 영향을 조사하였다. 세포 내 NO의 생성을 증가시키는 물질인 sodium nitroprusside (SNP)를 단독으로 처리하였을 때 SNP를 처리하지 않은 세포에 비교하여 PLD 활성은 0.5 mM 농도에서 2배 이상 증가하였다. 세포 내 cAMP의 농도를 증가시키는 물질인 dibutyryl-cAMP를 처리하였을 때 formyl-Met-Leu-Phe(fMLP)에 의한 PLD활성은 억제되었으나 cGMP를 증가시키는 물질인 8-bromo-cGMP(300 $\mu$M)를 단독으로나 fMLP와 같이 처리하였을 때 PLD의 활성은 큰 영향이 없었다. NO에 의한 PLD의 활성은 cGMP-의존형 인산화 효소인 protein kinase G(PKG)의 억제제인 KT 5823에 의하여 억제되지 않았는데 이러한 결과는 PKG 이외의 경로를 통하여 일어남을 제시한다. NO를 처리한 호중구에서 p38 mitogen activated protein kinase(MAPK)가 활성화되어 인산화된 p38 MAPK가 Western blot에서 증가되었다. NO에 의한 p38 MAPK의 인산화는 KT 5823에 의하여 억제되지 않았고 PLD 억제제인 n-butanol에 의하여도 영향을 받지 않았다. PLD 활성의 인자인 RhoA는 fMLP나 phorbol myristate acetate(PMA)의 자극에 의하여 세포질로부터 세포막으로 전이가 되었으나 cGMP의 전처리에 의하여 fMLP에 의한 RhoA의 전이는 억제되었으나 PMA에 의한 전이는 영향을 받지 않았다. 이들 결과들은 호중구 내 증가된 cGMP가 RhoA를 억제하였으나 세포 내 증가된 NO는 cGMP 이외의 인자를 통하여 PLD의 활성화를 일으킨다는 것을 제시하고 있다.

• BMB Reports
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• 제52권11호
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• pp.659-664
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• 2019

Vav1 is a Rho/Rac guanine nucleotide exchange factor primarily expressed in hematopoietic cells. In this study, we investigated the potential role of Vav1 in osteoclast (OC) differentiation by comparing the ability of bone marrow mononuclear cells (BMMCs) obtained from Vav1-deficient ($Vav1^{-/-}$) and wild-type (WT) mice to differentiate into mature OCs upon stimulation with macrophage colony stimulating factor and receptor activator of nuclear kappa B ligand in vitro. Our results suggested that Vav1 deficiency promoted the differentiation of BMMCs into OCs, as indicated by the increased expression of tartrate-resistant acid phosphatase, cathepsin K, and calcitonin receptor. Therefore, Vav1 may play a negative role in OC differentiation. This hypothesis was supported by the observation of more OCs in the femurs of $Vav1^{-/-}$ mice than in WT mice. Furthermore, the bone status of $Vav1^{-/-}$ mice was analyzed in situ and the femurs of $Vav1^{-/-}$ mice appeared abnormal, with poor bone density and fewer number of trabeculae. In addition, Vav1-deficient OCs showed stronger adhesion to vitronectin, an ${\alpha}_v{\beta}_3$ integrin ligand important in bone resorption. Thus, Vav1 may inhibit OC differentiation and protect against bone resorption.

• BMB Reports
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• 제51권6호
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• pp.296-301
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• 2018

Mitochondrial DNA (mtDNA) mutations are often observed in various cancer types. Although the correlation between mitochondrial dysfunction and cancer malignancy has been demonstrated by several studies, further research is required to elucidate the molecular mechanisms underlying accelerated tumor development and progression due to mitochondrial mutations. We generated an mtDNA-depleted cell line, ${\rho}^0$, via long-term ethidium bromide treatment to define the molecular mechanisms of tumor malignancy induced by mitochondrial dysfunction. Mitochondrial dysfunction in ${\rho}^0$ cells reduced drug-induced cell death and decreased the expression of pro-apoptotic proteins including p53. The p53 expression was reduced by activation of nuclear $factor-{\kappa}B$ that depended on elevated levels of free calcium in $HCT116/{\rho}^0$ cells. Overall, these data provide a novel mechanism for tumor development and drug resistance due to mitochondrial dysfunction.

• Journal of the Korean Society for Industrial and Applied Mathematics
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• 제11권4호
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• pp.9-17
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• 2007

Network Mobility basic support protocol (NEMO Basic) extends the operation of Mobile IPv6 to provide uninterrupted Internet connectivity to the communicating nodes of mobile networks. The protocol uses a mobile router (MR) in the mobile network to perform prefix scope binding updates with its home agent (HA) to establish a bi-directional tunnel between the HA and MR. This solution reduces location-update signaling by making network movements transparent to the mobile nodes (MNs) behind the MR. However, delays in data delivery and higher overheads are likely to occur because of sub-optimal routing and multiple encapsulation of data packets. To manage the mobility of the mobile network, it is important to minimize packet overhead, to optimize routing, and to reduce the volume of handoff signals over the nested mobile network. This paper proposes en aggregate router-assisted route optimization (ARARO) scheme for nested mobile networks support which introduces a local anchor router in order to localize handoff and to optimize routing. With ARARO, a mobile network node (MNN) behind a MR performs route optimization with a correspondent node (CN) as the MR sends a binding update message (BU) to aggregate router (AGR) via root-MR on behalf of all active MNNs when the mobile network moves. This paper describes the new architecture and mechanisms and provides simulation results which indicate that our proposal reduces transmission delay, handoff latency and signaling overhead. To evaluate the scheme, we present the results of simulation.

• BMB Reports
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• 제35권1호
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• pp.7-18
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• 2002

The major function of the thymus is to eliminate developing thymocytes that are potentially useless or autoreactive, and select only those that bear functional T cell antigen receptors (TCRs) through fastidious screening. It is believed that glucocorticoids (GCs) are at least in part responsible for cell death during death by neglect. In this review, we will mainly cover the topic of the GC-induced apoptosis of developing thymocytes. We will also discuss how thymocytes that are fated to die by GCs can be rescued from GC-induced apoptosis in. response to a variety of signals with antagonizing properties for GC receptor (GR) signaling. Currently, a lot of evidence supports the notion that the decision is made as a result of the integration of the multiple signal transduction networks that are triggered by GR, TCR, and Notch. A few candidate molecules at the converging point of these multiple signaling pathyways will be discussed. We will particularly describe the role of the SRG3 protein as a potent modulator of GC-induced apoptosis in the crosstalk.

• BMB Reports
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• 제54권12호
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• pp.626-631
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• 2021

Janus kinase 2 (JAK2), a non-receptor tyrosine kinase, is a critical component of cytokine and growth factor signaling pathways regulating hematopoietic cell proliferation. JAK2 mutations are associated with multiple myeloproliferative neoplasms. Although physiological and pathological functions of JAK2 in hematopoietic tissues are well-known, such functions of JAK2 in the nervous system are not well studied yet. The present study demonstrated that JAK2 could negatively regulate neuronal differentiation of mouse embryonic stem cells (ESCs). Depletion of JAK2 stimulated neuronal differentiation of mouse ESCs and activated glycogen synthase kinase 3β, Fyn, and cyclin-dependent kinase 5. Knockdown of JAK2 resulted in accumulation of GTP-bound Rac1, a Rho GTPase implicated in the regulation of cytoskeletal dynamics. These findings suggest that JAK2 might negatively regulate neuronal differentiation by suppressing the GSK-3β/Fyn/CDK5 signaling pathway responsible for morphological maturation.

• 대한의생명과학회지
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• 제20권2호
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• pp.49-55
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• 2014

RalBP1 is an ATP-dependent non-ABC transporter, responsible for the major transport function in many cells including many cancer cell lines, causing efflux of glutathione-electrophile conjugates of both endogenous metabolites and environmental toxins. RalBP1 is expressed in most human tissues, and is over-expressed in non-small cell lung cancer cell lines and in many other tumor types. Blockade of RalBP1 by various approaches has been shown to increase sensitivity to radiation and chemotherapeutic drugs, leading to cell apoptosis. In xenograft tumor models in mice, RalBP1 blockade or depletion results in complete and sustained regression across many cancer cell types including lung cancer cells. In addition to its transport function, RalBP1 has many other cellular and physiological functions, based on its domain structure which includes a unique Ral-binding domain and a RhoGAP catalytic domain, as well as docking sites for multiple signaling proteins. Additionally, RalBP1 is also important for stromal cell function in tumors, as it was recently shown to be required for efficient endothelial cell function and angiogenesis in solid tumors. In this review, we discuss the cellular and physiological functions of RalBP1 in normal and lung cancer cells.

• 생명과학회지
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• 제21권8호
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• pp.1134-1141
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• 2011

TMP21은 AD의 원인으로 작용하는 A${\beta}$-42 펩타이드 생성에 중요한 ${\gamma}$-secretase 활성을 억제하는 p24 family에 속하는 type I 막 단백질이다. 본 연구에서는 TMP21이 세포의 성장과 분화에 중요한 NGF 수용체 신호전달과정에 미치는 영향을 분석하고자 인간의 TMP21 cDNA를 합성하고, CMV promoter 조절 하에 hTMP21를 클로닝하여, CMV/hTMP21 벡터를 제조하였다. 그리고 이들 벡터를 B35 neuroblastoma에서 과발현시킨 후 ${\gamma}$-secretase 구성단백질과 NGF 수용체 연관 단백질의 변화를 관찰하였다. 그 결과, 4종류의 ${\gamma}$-secretase 구성단백질의 발현은 vehicle transfectants보다 CMV/hTMP21 transfectants에서 유의적으로 감소하였다. 또한 NGF low affinity 수용체인 $p75^{NTR}$과 downstream 단백질인 RhoA의 양은 NGF를 처리하지 않은 TMP21 transfectants에서 유의적으로 증가하였으나 NGF 처리에 의해 감소되었다. High affinity NGF 수용체인 TrkA의 인산화도 NGF 처리가 없는 경우 유의적으로 감소하였으나 NGF 처리에 의해 증가되었다. 또한 downstream 신호전달 과정 중에서 ERK의 인산화는 TrkA와 유사한 발현변화를 나타내었으나 Akt 인산화는 NGF의 처리에 의해 더욱 증가하였다. 이러한 결과는 TMP21이 neuroblastoma에서 NGF 수용체 신호전달과정를 조절하는 중요한 단백질로서 작용함을 제시하며, AD의 작용기전 연구에 중요한 기초자료를 제공할 것으로 사료된다.