• BMB Reports
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• 제45권12호
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• pp.700-706
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• 2012

Obesity is a worldwide epidemic as well as being a major risk factor for diabetes, cardiovascular diseases and several types of cancers. Obesity is mainly due to the overgrowth of adipose tissue arising from an imbalance between energy intake and energy expenditure. Adipose tissue, primarily composed of adipocytes, plays a key role in maintaining whole body energy homeostasis. In view of the treatment of obesity and obesity-related diseases, it is critical to understand the detailed signal transduction mechanisms of adipogenic differentiation. Adipogenic differentiation is tightly regulated by many key signal cascades, including insulin signaling. These signal cascades generally transfer or amplify the signal by using serial tyrosine phosphorylations. Thus, protein tyrosine kinases and protein tyrosine phosphatases are closely related to adipogenic differentiation. Compared to protein tyrosine kinases, protein tyrosine phosphatases have received little attention in adipogenic differentiation. This review aims to highlight the involvement of protein tyrosine phosphatases in adipogenic differentiation and the possibility of protein tyrosine phosphatases as drugs to target obesity.

• Archives of Pharmacal Research
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• 제24권5호
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• pp.446-454
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• 2001

Peptide fragments, isolated from proteolytic cleavage of thyroglobulin at specific sites, were examined for the iodination of tyrosine residues. The 50 kDa polypeptide, which was prepared from digestion of bovine thyroglobulin and continuous preparative SDS-PAGE, was subjected to reduction with DTT and alkylation with iodoacetic acid to generate S-car-boxymethylated peptide derivative, which was further hydrohysed by endoproteinase-Asp-N. Peptide products were separated by RP-HPLC, and each fraction was analyzed by LC/ESI-MS and MALDI-MS analyses. Based on the specificity of endoproteinase-Asp-N andthe mass spectra data, a peptide fragment turned out to correspond to a peptide, DALCCVKCPEGSYFQ (1438-1452), characterized by the presence of a thioredoxin box (CVKC) and a tyrosine residue. In addition, another peptide fragment (1453-1465) containing a thioredoxin box (CIPC) and a tyrosine residue was also observed. However, any evidence of iodination of the tyrosine residue present in these peptides was not provided. Meanwhile, tyrosine residues in the peptides, DVEEALAGKYLAGRFA (1366-1381) and DYSGLLLAFQVFLL (1290-1303) were found to be iodinated; mono- or diiodinated tyrosine residues, characteristic of a hormogenic site, existed in both peptides. In addition, the tyrosine residue in the peptide (1218-1252), corresponding to a hormonogenic site was also iodinated. Thus, there was a sharp difference of the susceptibility to oxidative iodination between the tyrosine residue in a hormonogenic site and that in a thioredoxin region. From these results, it is suggested that polypeptide region adjacent to tyrosine residues may govern the susceptibility of tyrosine to oxidative iodination.

• 한국식품영양학회지
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• 제9권1호
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• pp.21-28
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• 1996

This study was attempted to investigate the production of L-tyrosine by Brevibacterium flavum ATCC 14067. To select the strain which produce more L-tyrosine, mutants were induced by N-methyl-N'-nitro-nitrosoguanidine (NTG) treatment and phenylalanine auxotrophic mutants were induced by NTG and penicillin treatments. PFP resistant mutant was isolated from a phenylalanine auxotroph by retreatment with NTG and screened for increase of L-tyrosine production. PFP-326 mutant resistant to PPP (100ug/ml) was derived from phenylalanine auxotroph by mutagenesis with NTG and PFP-106 mutant resistant to PFP (1201g/ml) was derived from PFP-326 by mutagenesis with NTG. The composition of media for L-tyrosine production in strain PFP-106 was studied. PFP-106 mutant strain produced 50mg 11 of L-tyrosine while the parent strain produced 0.56mg 11 of L-tyrosine. The optimum composition of medium for L-tyrosine by strain PFP-106 was 10cA sucrose as carbon source, 3% ammonium sulfate as nitrogen source. The optimum cultural condition for producing L-tyrosine by strain PFP-106 was L-phenylalanine at a concentration of 1000g/mg.

• KSBB Journal
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• 제6권1호
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• pp.63-68
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• 1991

본 연구에서는 L-phcn ylalaninc을 생산하는 조절기작을 상실한 영양요구성 변이주인 Corynebacterium glulamicum ATCC 21674를 이용하여 플라스크내에서의 회분식 배양시의 특성을 조사하였다. 이 균주는 회분반효시 2.1-3.4 g/I 의 phcnllalanine파 2.9-4.4 g/I 의 tyrosine을 생산하였고, 당농도가 높을 경우 생산성이 저하됨을 알 수 있었다. 또한 온도의 변화는 이들 아미노산 생산에 큰 영향을 미침이 관찰되었다. $30^{\circ}C$에사 배양하는 경우, $37^{\circ}C$에서 배양하는 것보다 훨씬 많은 아미노산이 생산되었다. 배양도즙 pH는 급격한 변화를 보였다, 이 균주는 tyrosine이 없는 최소배지에서도 자라는 것이 확인되었고, tyrosine를 과량 생성까시 함으로 보아 영양 요구 성질을 상실한 revertant로서 조전기작 상실성을 ­유지한 것으로 판단된다.

• KSBB Journal
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• 제5권2호
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• pp.191-194
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• 1990

Tytosine은 방향족 아미노산이고, L-DOPA는 orth위치에 수산화기를 하나 더 가지는 tyrosine유도체이다. L-DOPA는 효소에 의하여 tyrosine으로부터 전환되어 생성할 수 있는데 반응액에서 두 물질을 분리, 분석하는 것은 상당히 어렵다. 본 논문에서는 두 아미노산 혼합물을 UV/VIS spetrophotermeter를 이용하여 동정함으로써 두 물질이 구분되는 두 파장을 결정하였고 두 파장에서 혼합물의 흡광도를 측정함으로써 농도를 정량하는 분석 system을 확립하였다. 이 방법은 사료에 아무런 전처리가 필요없으므로 손쉽고 간단하게 분석에 사용할 수 있다.

• BMB Reports
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• 제30권2호
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• pp.119-124
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• 1997

Transforming growth $factor-{\beta}\;(TGF-{\beta})$ is a multifunctional polypeptide that exerts biological roles including cell proliferation, differentiation, extracellular matrix deposition and apoptosis in many different cell types. $TGF-{\beta}$, although known as a negative growth regulator, has not been tested in human embryo lung (HEll cells. This study attempts to understand the role of $TGF-{\beta}$ on growth control of HEL cells in relationship to tyrosine phosphorylation pattern of cellular proteins. In density-arrested HEL cells treated with $TGF-{\beta}$, analysis of Western immunoblot showed induction of tyrosine phosphorylation of two major cellular proteins (15 kDa and 45 kDa). In normal proliferating HEL cells with different concentrations of serum, further analysis indicated that the increase in tyrosine phosphorylation of a 45 kDa protein was regulated in serum concentration-dependent manner. However, in proliferating HEL cells treated with $TGF-{\beta}$, tyrosine phosphorylation of 45 kDa was down-regulated. Calcium involvement in the regulation of tyrosine phosphorylation of 45 kDa and 15 kDa proteins was also examined. Tyrosine phosphorylation of 15 kDa protein but not of 45 kDa protein was regulated by exogenous calcium. The level of tyrosine phosphorylation of 15 kDa protein was low at reduced caclium concentration and high at elevated caclium concentration. $TGF-{\beta}$ reversed the pattern of tyrosine phosphorylation of 15 kDa protein. These results suggest that tyrosine phosphorylation of 45 and 15 kDa proteins in HEL cells may be controlled depending on the physiological status of the cells, i.e., low in arrested cells and high in proliferating cells. And the tyrosine phosphorylation of the two proteins appears to be down- or up-regulated by $TGF-{\beta}$.

• Journal of Microbiology and Biotechnology
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• 제18권2호
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• pp.365-368
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• 2008

Calcium entry through $Ca_v3.2Ca^{2+}$ channels plays essential roles for various physiological events including thalamic oscillation, muscle contraction, hormone secretion, and sperm acrosomal reaction. In this study, we examined how protein tyrosine phosphatases or protein tyrosine kinases affect $Ca_v3.2Ca^{2+}$ channels reconstituted in Xenopus oocytes. We found that $Ca_v3.2$ channel activity was reduced by 25% in response to phenylarsine oxide (tyrosine phosphatase inhibitor), whereas it was augmented by 19% in response to Tyr A47 or herbimycin A (tyrosine kinase inhibitors). However, other biophysical properties of $Ca_v3.2$ currents were not significantly changed by the drugs. These results imply that $Ca_v3.2$ channel activity is capable of being increased by activation of tyrosine phosphatases, but is decreased by activation of tyrosine kinases.

• 생명과학회지
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• 제15권3호
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• pp.492-498
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• 2005

PLDI 활성화 기전은 여러 보고가 있으나 PLD2 활성화에 대한 기전은 아직 연구의 대상이다. RBL-2H3 비만세포에서 HA-PLD2의 인산화 가능한 타이로신 잔기를 점돌연변이 시킨 DNA플라즈미드를 이용하여 11번, 14번, 470번의 타이로신이 항원자극에 의해 인산화 됨을 알아냈고 특히 470번 타이로신의 인산화가 PLD2 활성화에 중요하다는 결과를 얻었다.

• Applied Biological Chemistry
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• 제22권4호
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• pp.198-209
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• 1979

Esherichia intermedia A-21의 균체(菌體)에서 얻은 ${\beta}-tyrosinase$의 ${\alpha},{\beta}$-탈리작용(脫離作用)의 역(逆)반응을 이용하여 L-tyrosine, 2-chloro-L-tyrosine, 2-bromo-L-tyrosine 및 2-iodo-L-tyrosine을 효소합성하고 그들의 원소분석(元素分析)과 NMR-spectrum, Mass-spectrum 및 IR-spectrum을 측정하여 그 구조해석(構造解析)을 하였다. 또한 ${\beta}-tyrosinase$에 의한 각(各) halogen화(化) tyrosine의 합성속도와 분해속도 그리고 halogen화(化) phenol의 ${\beta}-tyrosinase$에 대한 저해작용(阻害作用) 및 2-bromotyrosine의 합성에서 m-bromophenol의 경시적(經時的) 첨가효과 등을 검토하여 다음과 같은 결과를 얻었다. 1) ${\beta}-tyrosinase$를 이용하여 pyruvin산(酸), $NH_3$ 그리고 m-chlorophenol, m-bromophenol 및 m-iodophenol 등을 기질로 한 각(各) halogen화(化) tyrosine의 효소합성에서 m-chlorophenol에서 2-chloro-tyrosine은 약 15%, m-bromophenol에서 2-bromotyrosine은 약 13.8% 그리고 m-iodophenol에서 2-iodotyrosine은 약 9.8%의 회수율(回收率)로 각각 얻어졌었다. 2) ${\beta}-tyrosinase$에 의한 tyrosine 및 halogen화(化) tyrosine의 합성에서 tyrosine의 합성속도를 100으로 하였을 때 2-chlorotyrosine은 28.2, 2-bromotyrosine은 8.13 그리고 2-iodotyrosine은 0.98의 상대속도를 보여 halogen화(化) tyrosine의 합성속도가 느렸다. 특히 Cl, Br, I의 순(順)으로 원자반경(原子半經)이 증가(增加)함에 따라서 halogen화(化) tyrosine의 합성속도가 저하(低下)되는 것이 인정(認定)되었다. 한편 3-iodotyrosine은 합성이 되지 않았다. 3) ${\beta}-tyrosinase$에 의한 tyrosine의 분해속도를 100으로 하였을 때 2-chlorotyrosine은 70.7, 2-bromotyrosine은 39.0, 2-iodotyrosine은 12.6의 상대적인 분해속도를 보였다. 즉 Cl, Br, I의 순(順)으로 원자반경(原子半經)이 크고 전기음성도(電氣陰性度)가 적어짐에 따라서 분해속도가 저하(低下)되는 것이 분명(分明)하였다 그리고 역시 3-iodotyrosine은 분해를 받지 않았다. 4) ${\beta}-tyrosinase$의 활성(活性)에 대하여 phenol은 현저한 조해작용(阻害作用)을 보였으며 o- 및 m-chlorophenol와 o-bromophenol의 조해(阻害)도 현저하였다. 반면 iodophenol의 조해(阻害)는 근소(僅少)하였으며 이들의 조해작용(阻害作用)을 Lineweaver-Burk plot법에 따라 측정한 결과 m-chlorophenol은 혼합형(混合型)의 조해작용(阻害作用)을 보였으며 그 Ki값은 $5.46{\times}10^{-4}M$이였다. 5) ${\beta}-tyrosinase$에 의한 2-bromotyrosine의 합성에서 기질인 m-bromophenol은 경시적(經時的)으로 소량(少量)씩 첨가하는 것이 효과적이었다. 6) ${\beta}-tyrosinase$를 이용하여 pyruvin산(酸), $NH_3$ 및 각(各) halogen화(化) phenol에서 합성한 2-halogen화(化) tyrosine들을 각각(各各) 원소분석(元素分析)하고 또한 NMR-spectrum, Mass-spectrum 그리고 IR-spectrum 등으로 측정하여 그들의 구조(構造)를 해석(解析)한 결과 각각(各各) 2-chloro-L-tyrosine, 2-bromo-L-tyrosine 및 2-iodo-L-tyrosine 임을 인정(認定)할 수 있었다.

• 생명과학회지
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• 제17권2호통권82호
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• pp.185-191
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• 2007

Akt/PKB는 세포의 증식, 분화, 사멸, 혈관신생 등 매우 많은 생리활성 조절에 있어 매우 중요한 역할을 수행한다. 우리는 Akt/PKB의 tyrosine잔기의 인산화가 $Thr^{\308}$ 인산화에 필수적임을 밝혔다. COS-7 세포주에 EGF를 처 리하면 Akt/PKB의 tyrosine 잔기에 인산화가 촉진되었으며 이러한 인산화 촉진은 Akt/PKB에 myristoylation site를 이용해 세포막으로 이동시키면 더욱 더 증가하였다. 특히, 분리된 Akt/PKB와 EGF 수용체를 이용해 인산화 반응을 실시하면 tyrosine잔기의 인산화뿐만 아니라 $Ser^{\473}$에 대한 인산화도 증가하였다. 더욱이 tyrosine잔기에 인산화 된 Akt/PKB는 활성화된 EGF 수용체와 직접적인 결합을 이루고 있음을 확인하였다. 마지막으로 예측되는 tyrosine 잔기인 $(Tyr^{\326})$을 Alanine으로 치환하면 정상 Akt/PKB뿐만 아니라 활성화된 Akt/PKB의 EGF에 의한 $Thr^{\308}$ 인산화가 사라짐을 확인하였다. 이러한 결과들을 바탕으로 EGF 수용체에 의한 직접적인 Akt/PKB의 tyrosine 인산화는 EGF에 의한 많은 생리활성 조절기전의 또 다른 기전이라 볼 수 있다.