• Journal of Integrative Natural Science
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• v.8 no.4
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• pp.285-292
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• 2015

LIM kinases belong to the serine/Threonine kinase family. The members of the LIM kinase (LIMK) family include LIMK 1 and 2 which are involved in the regulation of actin polymerisation and microtubule disassembly. LIMK1 was shown to be involved in cancer metastasis, while LIMK2 activation promotes cells cycle progression. Since LIMK2 plays a vital role in many disease conditions such as pulmonary hypertension, cancer and viral diseases, and till date there are not much selective inhibitors been reported, LIMK2 becomes an interesting therapeutic target among the kinases. 3D QSAR study was carried out on a series of pyrrolopyrimidines based derivatives as LIMK2 inhibitors. A reasonable CoMFA ($q^2$=0.888; ONC=3; $r^2$=0.974) with good statistical values was developed. The developed model was validated using 1000 runs of boostrapping and was found to be predictable. The results of CoMFA contour map analysis suggested that the bulky substitution at $R_4$ and $R_5$ position are highly desirable to increase the activity. Similarly, positive substitution at $R_3$ position is also required to increase the activity. It is also noted that bulky substitution at $R_1$ position must be avoided. Our results could provide valuable information to enhance the activity of the LIMK2 inhibitors and to design potent pyrrolopyrimidines derivatives.

• Bulletin of the Korean Chemical Society
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• v.34 no.9
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• pp.2829-2832
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• 2013

• Journal of Yeungnam Medical Science
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• v.37 no.4
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• pp.269-276
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• 2020

Fibrosis is characterized by excessive accumulation of extracellular matrix components. The fibrotic process ultimately leads to organ dysfunction and failure in chronic inflammatory and metabolic diseases such as pulmonary fibrosis, advanced kidney disease, and liver cirrhosis. Idiopathic pulmonary fibrosis (IPF) is a common form of progressive and chronic interstitial lung disease of unknown etiology. Pathophysiologically, the parenchyma of the lung alveoli, interstitium, and capillary endothelium becomes scarred and stiff, which makes breathing difficult because the lungs have to work harder to transfer oxygen and carbon dioxide between the alveolar space and bloodstream. The transforming growth factor beta (TGF-β) signaling pathway plays an important role in the pathogenesis of pulmonary fibrosis and scarring of the lung tissue. Recent clinical trials focused on the development of pharmacological agents that either directly or indirectly target kinases for the treatment of IPF. Therefore, to develop therapeutic targets for pulmonary fibrosis, it is essential to understand the key factors involved in the pathogenesis of pulmonary fibrosis and the underlying signaling pathway. The objective of this review is to discuss the role of kinase signaling cascades in the regulation of either TGF-β-dependent or other signaling pathways, including Rho-associated coiled-coil kinase, c-jun N-terminal kinase, extracellular signal-regulated kinase 5, and p90 ribosomal S6 kinase pathways, and potential therapeutic targets in IPF.

• Biomedical Science Letters
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• v.12 no.3
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• pp.201-208
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• 2006

PI3-kinase activity through p85, the regulatory subunit of class IA PI3-kinase, is indispensable for the growth, differentiation, and survival of skeletal muscle cells, but little is known about the function of other regulatory subunits such as p55 and p50. We examined the subcellular localization and the expression of the regulatory subunits of class IA PI3-kinase in L6 myoblasts. Both p55 and p50 as well as p85 were expressed in L6 myoblasts. Whereas p85 was localized at both cytosolic and nuclear tractions, p55 and p50 were localized at only the nuclear traction. During the differentiation of L6 myoblasts, the protein concentrations of both p55 and p50 were decreased but that of p85 was not significantly changed. Menadione-induced oxidative stress induced the translocation of p85 from cytosol to nucleus and the increase of p55 expression. These results suggest that the regulatory subunits of class IA PI3-kinase play an important role in L6 myoblasts.

• 한국생물공학회:학술대회논문집
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• 2005.04a
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• pp.509-509
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• 2005

• Archives of Pharmacal Research
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• v.18 no.4
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• pp.262-266
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• 1995

Bacterial lipopolysaccharide (LPS) is one of the most potent inducers of various cytokines nad other proinflammatory mediators in macrophages. Although pathophysiological consequences of LPS-induced responses are well established, the mechanisms through which LPS-generated singals are transduced remain unclear. In the present study, we attempted to determine early intracellular events after LPS binding which transduced the signal for the induction of arachidonic acid metabolism in rat alveolar macrophages. While H-7, a protein kinase C(PKC) inhibitor, did not affect LPS-stimulated prostaglandin synthesis, staurosporine enhanced archidonic acid etabolism in macropahages treated with LPS. Phorbol-12-myristate-13 acetate snesitive to LPS compare with control group. PMA and H-7 did not alter the effect of flucose. Pertussis toxin did not show nay effect, thus pertussis toxin snesitive G-protein pathway appears not to play a role in this experimental system. Genistein and tyrphostin 25, protein tyrosine kinase 9PTK) inhibitors, markedly inhibited prostaglandin synthesis in macrophages nal transduction events leading to icnreased macrophage arachidonic acid metabolism.

• Genomics & Informatics
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• v.8 no.2
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• pp.90-93
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• 2010

A-kinase-anchoring proteins (AKAPs) are scaffold proteins which compartmentalize protein kinase A (PKA, cAMP-dependent protein kinase) and other enzymes to specific subcellular sites. The spatiotemporal control of these enzymes by AKAPs is important for cellular function like cell growth and development etc. Hence, it is important to understand the basic function of AKAPs and their functional domains. However, diverse names, function, cellular localizations and many members of AKAPs increase difficulties when researchers search appropriate AKAPs for their experimental purpose. Nevertheless, there was no previous AKAPs-related database regardless of their important cellular functions and difficulty of finding appropriate AKAPs. So, we developed AKAPs database (AKAPDB), which contains their sequence information, functions and other information derived from prediction programs and other databases. Therefore, we propose that AKAPDB can be an important tool to researchers in the related fields. AKAPDB is available via the internet at http://plaza3.snu.ac.kr/akapdb/.

• Bulletin of the Korean Chemical Society
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• v.28 no.8
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• pp.1413-1415
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• 2007

• Journal of Yeungnam Medical Science
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• v.7 no.1
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• pp.39-50
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• 1990

The one event on signalling mechanism is the cleavage by adenyl cyclase of ATP into second messenger, cyclic AMP. The other transfer system of inositol metabolism. it is widely recognized that hydrolysis of the minor membrane lipid phosphoinositide bisphosphate($PIP_2$) initiated by occupation of certain receptors and catalyzed by phospholipase C, lead to toe generation of the two intracellular messengers, inositol triphosphate($IP_3$) and diacylglycerol(DG). $IP_3$ is converted to inositol tetrakisphosphate($IP_4$) by $IP_3$ kinase. In the present study, it is that purification of calmodulin is used by phenyl-Sepharose CL-4B chromatography. it's molecular weigh, 17.000 in SDS-polyacrylamide gel electrophoresis. In order to observe the affinity between calmodulin (CaM)-Affigel 15 and $IP_3$ kinase, and isolated $IP_3$ kinase, was applied in CaM-Affigel with $Ca^{2+}$ equilibirum buffer and EGTA equilibirum buffer. We compared with binding and elution effect of $IP_3$ kinase in several condition of buffer. In affinity of binding. $Ca^{2+}$ equilibrium buffer was in the most proper condition. and elution, CaM/$Ca^{2+}$ buffer(CE1 10.36, CE2 12. 76pM/min/mg of protein) was effected much more than EGTA buffer(E2 1.48, E3 2.43pM/min/mg of protein), but CaM/$Ca^{2+}$ stimulate the activity of $IP_3$ kinase. And then, several detergents such as sodium deoxycholate, tween 20. cholic acid, polyethylene glycol, chaps were applied. The 0.2% chaps buffer(E2 23.19, E3 8.05pM/min/mg of protein) was the most effective in elution of $IP_3$ kinase.

• 한국생물공학회:학술대회논문집
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• 2005.04a
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• pp.515-515
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• 2005