• 한국동물학회지
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• 제33권2호
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• pp.141-151
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• 1990

Raf protein kinases and protein kinase C는 세포질내 serine/threonine-specific protein에 속한다. 그리고 기능적인 구조와 세포내의 분포 양상은 서로 비슷하다. Raf family oncogene를 발현시키는 a-raf와 c-raf protein kinase에 대한 antibodies로써 남생이 대뇌의 raf protein kinase의 분포를 조사하였다. 일반적으로 raf protein kinase는 제한된 지역에서 즉,general pallium,hippocampal formation, pdmordiuin hippocampi,nucleus of lateral olfactory tract, basal amygdaloid nucleus와bed of stria terminalis에 나타났으며, c-raf protein kinase의 면역학적 labeling은 a-raf보다 그 범위가 넓었다. 그렇지만 labeling되는 intensity는 오히려 a-raf보다 낮았다. 그런데 a-raf에서 가장 명확한 좋은 예는 basal amygdaloid nucleus내의 구형모양의 세포인데, 이 세포는 세포질이 매우 강하게 labeling되어 지므로 ring모양과 같이 나타났다. 특히 c-raf는 protein kinase C 가 많이 나타나는 pyramidal 세포나 Purkinje세포에 많이 존재하는 것을 볼 때 protein kinase에 의하여 활성화되는 myc와 서로 상협작용을 유도한다고 제안하는 바이다.

• Bulletin of the Korean Chemical Society
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• 제33권5호
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• pp.1571-1576
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• 2012

A diarylurea compound 1 possessing pyrrolo[3,2-$c$]pyridine nucleus was designed and synthesized with structure similarity to Sorafenib. Compound 1 was tested over 60-cancer cell line panel at a single dose concentration of 10 ${\mu}M$ and showed high activity. It was further tested in a five-dose mode to determine its $IC_{50}$, TGI, and $LC_{50}$ values over the 60 cell lines. Compound 1 showed high potency and good efficacy, and was accordingly tested at a single dose concentration of 10 ${\mu}M$ over a panel of 40 kinases. At this concentration, it completely inhibited the enzymatic activities of a number of oncogenic kinases, including ABL, ALK, c-RAF, FLT3, KDR, and TrkB. The target compound was subsequently tested over these 6 kinases in 10-dose testing mode in order to determine its $IC_{50}$ values.

• Biotechnology and Bioprocess Engineering:BBE
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• 제10권6호
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• pp.535-539
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• 2005

The thermoacidophilic archaeon Thermoplasma acidophilum has long been known to utilize D-glucose via the non-phosphorylated Entner-Doudoroff (nED) pathway. We now report the identification of a gene encoding 2-keto-3-deoxy-D-gluconate (KDG) kinase. The discovery of this gene implies the presence of a glycolysis pathway, other than the nED pathway. It was found that Ta0122 in the T. acidophilum genome corresponded to KDG kinase. This enzyme shares no similarity with known KDG kinases, and belongs to a novel class of sugar kinases. Of the five sugars tested only KDG was utilized as a substrate.

• Bulletin of the Korean Chemical Society
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• 제35권7호
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• pp.2123-2129
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• 2014

Pim kinases are promising targets in the treatment of hematopoietic and solid cancers. Meridianin C was chosen as a starting point to discover novel pim kinase inhibitors. Using known pim kinase's structural information, aminopyrimidine was introduced to provide the hydrogen-bonding interactions with the conserved lysine residue in the ATP binding pocket of all three Pim kinases. Synthesized 3,5-bis(aminopyrimidinyl)indole derivatives showed pan-pim inhibitory activity. Aminoalkyl substituent was attached on the aminopyrimidine to further enhance the potency and physicochemical properties of compound. The research reveals a significative way of designing compounds with high potency and kinase selectivity for pan-pim kinases.

• Archives of Pharmacal Research
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• 제21권5호
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• pp.487-495
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• 1998

Gorwth factors such as TGF-beta, PDGF and FGF are thought to play important roles in wound healing. However, thier biological activity and signal transduction during wound repair remain poorly understood. Growth factors are often ligands for receptor tyrosine kinase and receptor serine/threonine kinases. With recent advances in signal transduction by receptor kinases, we are beginning to understand the underlying mechanism of how growth factors may regulate cutaneous wound repair. In this paper, we will describe the pharmacological effects of growth factors on wound healing, and dscuss the potential underlying signaing mechanisms. thus, we hope to provide the basis for designing more specific therapeutics for wound healing in the near future.

• Quantitative Bio-Science
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• 제37권2호
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• pp.113-124
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• 2018

Pim kinases are important targets for cancer therapies because they are mainly responsible for cancer metastasis and overall therapeutic treatment responses. Because of their unusual structural feature in the hinge region of the ATP-binding site, new binding motifs have been discovered and used for the development of Pim kinases inhibitors. The results of a screening of 5-membered heteroaromatic compounds and the effects of structural modifications on the inhibition of Pim kinases' activities showed the potential scaffold for Pim inhibitors. 1,3,4-Oxadiazole-2(3H)-thione was found as a new scaffold for Pim kinase inhibitors.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.187.2-187.2
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• 2003

The cyclin-dependent kinases (CDKs), a group of serine/threonine kinases that form active heterodimeric complexes binding to cyclins, are key regulators of the cell cycle. The role of cyclin dependent kinases(CDKs) in cell cycle regulation has stimulated an interest in them as potential targets for proliferative diseases such as cancer, psoriasis, and chemotherapeutic agent-induced alopecia. Indirubin, an active ingredient of a traditional Chinese recipe Danggui Longhui Wan, are potent CDK inhibitors competing with ATP for binding to the catalytic site of the CDKs. (omitted)

• 생명과학회지
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• 제18권1호
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• pp.114-119
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• 2008

Wee1 인산화효소는 세포주기 조절의 핵심 단백질인 cdc2/cyclinB 복합체를 인산화하여 활성을 억제, 조절하는 주요한 효소이다. 지금까지 포유동물에서는 Wee1A, Wee1B 그리고 Myt1의 세 가지 효소가 발견되었다. Wee1 인산화효소의 조절기작을 연구하기 위하여 생쥐의 Wee1A와 Wee1B를 발톱개구리의 난자에 주사한 후 단백질의 변형을 관찰하였다. 이 세포주기 과정에서 두 효소는 모두 인산화 되었으며, Wee1A단백질은 분해되는 것을 관찰 할 수 있었다. 또한 세포외 인산화 방법을 통하여 Wee1A가 PKA와 Akt에 의해 인산화됨을 확인하였다. 이러한 Wee1 인산화효소의 인산화와 단백질 안정성에 영향을 미치는 단백질 내의 부위를 살펴보고자, Wee1A와 Wee1B의 아미노 도메인과 카르복실 도메인을 서로 치환한 단백질을 제조하여 개구리 난자에 주사하고 인산화 정도와 단백질의 안정성을 조사하였을 때, Wee1A의 아미노 도메인이 단백질의 인산화와 안정화에 중요한 영향을 미친다는 것을 규명하였다. 그리고 Wee1B의 아미노 도메인과 Wee1A의 카르복실 도메인은 효소의 활성을 조절하는 역할을 한다.

• Journal of Photoscience
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• 제9권2호
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• pp.229-232
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• 2002

There are two distinct UV-responsive signaling pathways in UV-irradiated mammalian cells, i.e., the DNA damage-dependent and -independent pathways. The former occurs in nucleus and results in growth arrest and apoptosis via post-translational modification of p53. The latter is initiated by oxidative stress and/or by damages in cell membrane or cytoplasm, which activate signaling cascade through intracellular molecules including mitogen activated protein kinases (MAPK). In normal human fibroblastic cells, all of MAPK family members, extracellular signal-related kinases (ERK), c-Jun N-terminal kinases (JNK) and p38, were rapidly phosphorylated following UV-irradiation. ERK phosphorylation was suppressed by an inhibitor of receptor tyrosine kinases (RTK). As ERK usually responds to mitogenic stimuli from RTK ligands, UV-induced ERK phosphorylation may be linked to the proliferation of survived cells. In contrast, phosphorylation of JNK and p38, as well as apoptosis, were modulated by the level of UV-generated oxidative stress Therefore, JNK and p38 may take part in oxidative stress-mediated apoptosis. Phosphorylation of p53 at Ser and Thr residues are essential for stabilization and activation of p53. Among several sites reported, we confirmed phosphorylation at Ser-15 and Ser-392 after UV-irradiation. Both of these were inhibited by a phosphoinositide 3-kinase inhibitor, presumably due to the shutdown of signals from DNA damage to p53. Phosphorylation at Ser-392 was also sensitive to an antioxidant and a p38 inhibitor, suggesting that Ser-392 of p53 is one of the possible points where DNA damage-dependent and -independent apoptic signals merge. Thus, MAPK pathway links UV-induced intracellular signals to the nuclear responses and modifies DNA damage-dependent cellular outcome, resulting in the determination of cell death.

• 한국자원식물학회지
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• 제32권6호
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• pp.633-643
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• 2019

Long-term ultraviolet (UV) exposure accelerates the phenomenon of skin photo-aging by activating collagenase and elastase. In this study, we aimed to investigate the effects of a combination of grapefruit and rosemary extracts (cG&Re) on UVB-irradiated damage in HaCaT cells and dorsal mouse skin. In HaCaT cells, cG&Re recovered UVB-reduced cell viability and inhibited protein expression of mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinases (p-Erk), c-Jun N-terminal kinases (p-JNK), and a class of MAPKs (p-P38). Also, cG&Re suppressed UVB-induced collagen and elastin degradation by decreasing matrix metalloproteinases (MMPs) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB) expression, which is a transcription factor. Similar results were observed in dorsal mouse skin. Taken together, our data indicate that cG&Re prevent UVB-induced skin photo-aging due to collagen/elastin degradation via activation of MAPKs, MMPs, and the NF-κB signaling pathway in vitro and in vivo.