Oligomerization and multimerization are critical for angiopoietin-1 to bind and phosphorylate Tie2 = Angiopoietin-1의 Tie2 수용체에 대한 결합과 인산화를 위해 요구되는 Angiopoietin-1의 다중화에 대한 연구

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Angiopoietin-1 (Ang1) is an essential molecule for blood vessel formation. However, little is known about the structure-function relationships of Ang1 with its receptor, Tie2 (tyrosine kinase with immunoglobulin and epidermal growth factor homology domain-2). Ang1 and Angiopoietin-2 (Ang2) variants was generated to define the role of the superclustering and oligomerization domains of the Ang1 protein. Then the molecular structure of the variants was analyzed with SDS-PAGE and rotary metal-shadowing transmission electron microscopy (RMSTEM) and the effects of these variants on the binding and activation of Tie2 were determined. Ang1 exists as heterogeneous multimers with basic trimeric, tetrameric, and pentameric oligomers, whereas Ang2 exists as trimeric, tetrameric, and pentameric oligomers. The variant Ang1C265S, consisting of trimers, tetramers, and pentamers without multimeric forms of Ang1, yielded less Tie2 activation than did Ang1, whereas monomeric Ang1 (Ang1/FD), dimeric Ang1 variants (Ang1D2, and Ang1D3), and dimeric and trimeric Ang1 variant (Ang1D1) dramatically lost their ability to bind and activate Tie2. An Ang1 protein in which two cysteines (amino acids #41 and #54) were replaced with serines (Ang1C41S/C54S) formed mostly dimers and trimers that were not able to bind and activate Tie2. In addition, improper creation of a new cysteine in Ang2 (Ang2S263C) dramatically induced oligomerization of Ang2 like Ang1 without activating Tie2. In conclusion, proper oligomerization of Ang1 having at least four subunits by the intermolecular disulfide linkage involving cysteines 41 and 54 is critical for Tie2 binding and activation.
Advisors
Koh, Gou-Youngresearcher고규영researcher
Description
한국과학기술원 : 생명과학과,
Publisher
한국과학기술원
Issue Date
2006
Identifier
255236/325007  / 020037905
Language
eng
Description

학위논문(석사) - 한국과학기술원 : 생명과학과, 2006.2, [ iii, 46 p. ]

Keywords

oligomerization/multimerization; Angiopoietin; Tie2; 혈관신생; 다중체화; 안지오포이에틴; angiogenesis

URI
http://hdl.handle.net/10203/28073
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=255236&flag=dissertation
Appears in Collection
BS-Theses_Master(석사논문)
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