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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 충북대학교 동물의학연구소 Journal of Biomedical and Translational Research Journal of Biomedical and Translational Research 제18권 제2호
- 발행연도
- 2017.6
- 수록면
- 43 - 49 (7page)
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초록· 키워드
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The p21-activated kinases (PAKs) are a family of serine/threonine protein kinases and activated by binding with activated Rho GTPases such as Rac or Cdc42. PAKs regulate actin cytoskeletal remodeling, cell motility, cell survival, and apoptosis. Also, PAKs are involved in several diseases such as cancer, virus infectious diseases, mental retardation, Alzheimer and Parkinson's diseases. Therefore, the substances that are able to inhibit PAK activation can be used as powerful tools and medicines for PAK relative diseases or specific inhibitors for study of PAK signaling pathway. In this study, we investigated and characterized the 5 compounds of 4-benzene-1, 2-naphthoquinone (NQ) family as candidate substances to inhibit the PAK1 activation in vitro and in cells. Binding between p21-binding domain (PBD) of PAK1 and Cdc42 was blocked by 5 NQ-compounds in ELISA assay. Myelin basic protein (MBP) phosphorylation was dramatically reduced by treatment of these compounds in vitro kinase assay for Cdc42-induced or constitutive active PAK1 mutant. Also, phosphorylation at Thr 423 of transfected PAK1 was inhibited by treatment of 5 NQ-compounds in 293T cells, respectively. Finally, NQ-5 inhibited strongly the PAK1 activation by PDGF stimulation and cell motility in PDGF-induced wound migration assay in NIH 3T3 cells. Therefore, these NQ compounds will be good candidates as target molecules to regulate PAK1-related diseases or inhibitors to study PAK1 signaling pathway.
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참고문헌 (27)
참고문헌 신청
Manser E / 1994 / A brain serine/threonine protein kinase activated by Cdc42 and Rac1 / Nature 367:40~46
Jaffer ZM / 2002 / p21-activated kinases : three more join the Pak / Int J Biochem Cell B 34:713~717
Beeser A / 2005 / Role of group A p21-activated kinases in activation of extracellular-regulated kinase by growth factors / J Biol Chem 280:36609~36615
Bokoch GM / 2003 / Biology of the p21-activated kinases / Ann Rev Biochem 72:743~781
Lei M / 2000 / Harrison SC : Structure of PAK1 in an autoinhibited conformation reveals a multistage activation switch / Cell 102:387~397
Jaffer ZM / 2002 / p21-activated kinases : three more join the Pak / Int J Biochem Cell B 34:713~717
Beeser A / 2005 / Role of group A p21-activated kinases in activation of extracellular-regulated kinase by growth factors / J Biol Chem 280:36609~36615
Bokoch GM / 2003 / Biology of the p21-activated kinases / Ann Rev Biochem 72:743~781
Lei M / 2000 / Harrison SC : Structure of PAK1 in an autoinhibited conformation reveals a multistage activation switch / Cell 102:387~397
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