title: Gln-362 of angiopoietin-2 mediates migration of tumor and endothelial cells through association with α5β1 integrin.
abstract: Angiopoietin-2 (Ang-2) not only regulates angiogenesis by binding to its well known receptor Tie2 on endothelial cells but also controls sprouting of Tie2-negative angiogenic endothelial cells and invasion of Tie2-negative non-endothelial cells by binding to integrins. However, the molecular mechanism of the Ang-2/integrin association has been unclear. In this study, we found that the Gln-362 residue of Ang-2 was essential for binding to α5β1 integrin. A Q362E Ang-2 mutant, which still bound to Tie2, failed to associate with α5β1 integrin and was unable to activate the integrin downstream signaling of focal adhesion kinase. In addition, unlike wild-type Ang-2, the Q362E Ang-2 mutant was defective in mediating invasion of Tie2-negative glioma or Tie2-positive endothelial cells. Furthermore, the tailpiece domain of the α5 subunit in α5β1 integrin was critical for binding to Ang-2. Taken together, these results provide a novel insight into the mechanism of integrin regulation by Ang-2, which contributes to tumor invasion and endothelial cell migration in a Tie2-independent manner.
authors.affiliation: From the Bio Therapeutics Lab, Samsung Advanced Institute of Technology, Samsung Electronics Co., Ltd., 130 Samsung-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do 443-803, South Korea.
authors.forename: Hyo Seon
authors.initials: HS
authors.lastname: Lee
authors.affiliation: From the Bio Therapeutics Lab, Samsung Advanced Institute of Technology, Samsung Electronics Co., Ltd., 130 Samsung-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do 443-803, South Korea.
authors.forename: Seung Ja
authors.initials: SJ
authors.lastname: Oh
authors.affiliation: From the Bio Therapeutics Lab, Samsung Advanced Institute of Technology, Samsung Electronics Co., Ltd., 130 Samsung-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do 443-803, South Korea.
authors.forename: Kwang-Hoon
authors.initials: KH
authors.lastname: Lee
authors.affiliation: From the Bio Therapeutics Lab, Samsung Advanced Institute of Technology, Samsung Electronics Co., Ltd., 130 Samsung-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do 443-803, South Korea.
authors.forename: Yoon-Sook
authors.initials: YS
authors.lastname: Lee
authors.affiliation: From the Bio Therapeutics Lab, Samsung Advanced Institute of Technology, Samsung Electronics Co., Ltd., 130 Samsung-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do 443-803, South Korea.
authors.forename: Eun
authors.initials: E
authors.lastname: Ko
authors.affiliation: From the Bio Therapeutics Lab, Samsung Advanced Institute of Technology, Samsung Electronics Co., Ltd., 130 Samsung-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do 443-803, South Korea.
authors.forename: Kyung Eun
authors.initials: KE
authors.lastname: Kim
authors.affiliation: From the Bio Therapeutics Lab, Samsung Advanced Institute of Technology, Samsung Electronics Co., Ltd., 130 Samsung-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do 443-803, South Korea.
authors.forename: Hyung-chan
authors.initials: HC
authors.lastname: Kim
authors.affiliation: From the Bio Therapeutics Lab, Samsung Advanced Institute of Technology, Samsung Electronics Co., Ltd., 130 Samsung-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do 443-803, South Korea.
authors.forename: Seokkyun
authors.initials: S
authors.lastname: Kim
authors.affiliation: From the Bio Therapeutics Lab, Samsung Advanced Institute of Technology, Samsung Electronics Co., Ltd., 130 Samsung-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do 443-803, South Korea.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Song
authors.affiliation: the Well Aging Center, Samsung Advanced Institute of Technology, Samsung Electronics Co., Ltd., Suwon-Si 443-803, South Korea, and.
authors.forename: Yong-In
authors.initials: YI
authors.lastname: Kim
authors.affiliation: From the Bio Therapeutics Lab, Samsung Advanced Institute of Technology, Samsung Electronics Co., Ltd., 130 Samsung-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do 443-803, South Korea, the School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, South Korea chungho@korea.ac.kr.
authors.forename: Chungho
authors.initials: C
authors.lastname: Kim
authors.affiliation: From the Bio Therapeutics Lab, Samsung Advanced Institute of Technology, Samsung Electronics Co., Ltd., 130 Samsung-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do 443-803, South Korea, sangyeul.han@samsung.com.
authors.forename: Sangyeul
authors.initials: S
authors.lastname: Han
mesh_terms: D042702:Angiopoietin-2 / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D006224:Cricetinae; D003412:Cricetulus; D042783:Endothelial Cells / Q000166:cytology*; D005786:Gene Expression Regulation; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D042787:Receptor, TIE-2 / Q000378:metabolism*
chemical_list: D042702:Angiopoietin-2; D039081:Integrin alpha5beta1; D016023:Integrins; D005973:Glutamine; D042787:Receptor, TIE-2
keywords: Angiogenesis; Angiopoietin-2; Cell Invasion; Cell Migration; Endothelial Cell; Integrin; Tie2