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Human MST2 인산화효소의 기질 특이성에 관한 연구
Characterization of the substrate specificity of human MST2 kinase

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Authors
배수진
Advisor
최희정
Major
자연과학대학 생명과학부
Issue Date
2016-02
Publisher
서울대학교 대학원
Keywords
MST2 kinase structureLATS kinaseMOB1YAP1Hippo signaling pathwayMST2 specificity
Description
학위논문 (석사)-- 서울대학교 대학원 : 생명과학부, 2016. 2. 최희정.
Abstract
Mammalian Hippo signaling plays an important role in controlling organ size by regulating cell growth, proliferation and apoptosis. Dysregulation of this pathway is implicated in several human diseases including cancer. MST2 (also known as STK3/Hpo in Drosophila) is an upstream kinase in the Hippo signaling pathway, to activate LATS1 kinase, which in turn phosphorylates and inactivates a transcriptional coactivator, YAP (Yes associated protein), Previous structural study of the MST2 kinase domain showed that it forms a canonical kinase fold. However, it did not explain the substrate specificity of MST2 kinase and the molecular mechanism of substrate binding. Here, to investigate substrate specificity of MST2 kinase, we performed in vitro kinase assays using the several different substrates, including MOB1, LATS1, and YAP1. Unexpectedly, YAP1 as well as YAP1 peptide containing well-known phosphorylation site, Ser127, were readily phosphorylated by MST2. LATS1, a cellular substrate of MST2 was phosphorylated by MST2, whereas LATS1 peptide including Thr1079 could not be phosphorylated, implying for the importance of three dimensional structure of the substrate in some cases. Sequence analysis of various substrates suggests that there is no consensus sequence motif for MST2 kinase but the presence of at least one or more basic amino acids surrounding the phosphorylation site is highly preferred. These results will greatly improve our understanding of substrate specificity of MST2 kinase and be helpful for future structural study of the MST2-substrate complexes.
Language
Korean
URI
http://hdl.handle.net/10371/131602
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College of Natural Sciences (자연과학대학)Dept. of Biological Sciences (생명과학부)Theses (Master's Degree_생명과학부)
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