Anti‐FGF23 Neutralizing Antibodies Show the Physiological Role and Structural Features of FGF231* (original) (raw)
Journal Article
,
These authors contributed equally to this work
Discovery Research Laboratories, Kirin Pharma, Gunma, Japan
Search for other works by this author on:
,
Quantum Beam Science Directorate, Japan Atomic Energy Agency, Ibaraki, Japan
These authors contributed equally to this work
Search for other works by this author on:
,
Development Research Laboratories, Kirin Pharma, Gunma, Japan
These authors contributed equally to this work
Search for other works by this author on:
,
Discovery Research Laboratories, Kirin Pharma, Gunma, Japan
Search for other works by this author on:
,
Discovery Research Laboratories, Kirin Pharma, Gunma, Japan
Search for other works by this author on:
,
Discovery Research Laboratories, Kirin Pharma, Gunma, Japan
Search for other works by this author on:
,
Division of Nephrology and Endocrinology, Department of Medicine, The University of Tokyo Hospital, Tokyo, Japan
Search for other works by this author on:
,
Quantum Beam Science Directorate, Japan Atomic Energy Agency, Ibaraki, Japan
Search for other works by this author on:
,
Discovery Research Laboratories, Kirin Pharma, Gunma, Japan
Search for other works by this author on:
,
Division of Nephrology and Endocrinology, Department of Medicine, The University of Tokyo Hospital, Tokyo, Japan
Search for other works by this author on:
Received:
09 November 2007
Revision received:
21 March 2008
Published:
04 December 2009
Cite
Yuji Yamazaki, Taro Tamada, Noriyuki Kasai, Itaru Urakawa, Yukiko Aono, Hisashi Hasegawa, Toshiro Fujita, Ryota Kuroki, Takeyoshi Yamashita, Seiji Fukumoto, Takashi Shimada, Anti‐FGF23 Neutralizing Antibodies Show the Physiological Role and Structural Features of FGF23, Journal of Bone and Mineral Research, Volume 23, Issue 9, 1 September 2008, Pages 1509–1518, https://doi.org/10.1359/jbmr.080417
Close
Navbar Search Filter Mobile Enter search term Search
Abstract
Fibroblast growth factor (FGF)23 is proposed to play a physiological role in the regulation of phosphate and vitamin D metabolism; deranged circulatory levels of FGF23 cause several diseases with abnormal mineral metabolism. This paper presents a novel approach to analyze the mechanism of action of FGF23 using anti‐FGF23 monoclonal antibodies that can neutralize FGF23 activities both in vitro and in vivo. We developed two antibodies (FN1 and FC1) that recognize the N‐ and C‐terminal regions of FGF23, respectively. Both FN1 and FC1 inhibited FGF23 activity in a cell‐based Klotho‐dependent reporter assay. Their administration caused marked increases in serum phosphate and 1,25D levels in normal mice. These changes were accompanied by altered expression in the kidney of type IIa sodium‐phosphate cotransporter, 25‐hydroxyvitamin‐D‐1α‐hydroxylase, and 24‐hydroxylase. Thus, this study using neutralizing antibodies confirms that FGF23 is a physiological regulator of phosphate and vitamin D metabolism. We addressed the mechanism of action for these neutralizing antibodies. Structural analysis of the FGF23/FN1‐Fab complex showed that FN1 masked putative FGF receptor‐binding sites in the N‐terminal domain of FGF23, whereas biochemical analyses showed that FC1 interfered with the association between FGF23 and Klotho by binding to the C‐terminal domain of FGF23. Taken together, our results suggest that the N‐ and C‐terminal domains of FGF23 are responsible for association with cognate FGF receptors and Klotho, respectively, and that these interactions are indispensable for FGF23 activity.
Copyright © 2008 ASBMR
You do not currently have access to this article.
Personal account
- Sign in with email/username & password
- Get email alerts
- Save searches
- Purchase content
- Activate your purchase/trial code
- Add your ORCID iD
Get help with access
Institutional access
Access to content on Oxford Academic is often provided through institutional subscriptions and purchases. If you are a member of an institution with an active account, you may be able to access content in one of the following ways:
IP based access
Typically, access is provided across an institutional network to a range of IP addresses. This authentication occurs automatically, and it is not possible to sign out of an IP authenticated account.
Sign in through your institution
Choose this option to get remote access when outside your institution. Shibboleth/Open Athens technology is used to provide single sign-on between your institution’s website and Oxford Academic.
- Click Sign in through your institution.
- Select your institution from the list provided, which will take you to your institution's website to sign in.
- When on the institution site, please use the credentials provided by your institution. Do not use an Oxford Academic personal account.
- Following successful sign in, you will be returned to Oxford Academic.
If your institution is not listed or you cannot sign in to your institution’s website, please contact your librarian or administrator.
Sign in with a library card
Enter your library card number to sign in. If you cannot sign in, please contact your librarian.
Society Members
Society member access to a journal is achieved in one of the following ways:
Sign in through society site
Many societies offer single sign-on between the society website and Oxford Academic. If you see ‘Sign in through society site’ in the sign in pane within a journal:
- Click Sign in through society site.
- When on the society site, please use the credentials provided by that society. Do not use an Oxford Academic personal account.
- Following successful sign in, you will be returned to Oxford Academic.
If you do not have a society account or have forgotten your username or password, please contact your society.
Sign in using a personal account
Some societies use Oxford Academic personal accounts to provide access to their members. See below.
Personal account
A personal account can be used to get email alerts, save searches, purchase content, and activate subscriptions.
Some societies use Oxford Academic personal accounts to provide access to their members.
Viewing your signed in accounts
Click the account icon in the top right to:
- View your signed in personal account and access account management features.
- View the institutional accounts that are providing access.
Signed in but can't access content
Oxford Academic is home to a wide variety of products. The institutional subscription may not cover the content that you are trying to access. If you believe you should have access to that content, please contact your librarian.
Institutional account management
For librarians and administrators, your personal account also provides access to institutional account management. Here you will find options to view and activate subscriptions, manage institutional settings and access options, access usage statistics, and more.
Purchase
Short-term Access
To purchase short-term access, please sign in to your personal account above.
Don't already have a personal account? Register
Anti‐FGF23 Neutralizing Antibodies Show the Physiological Role and Structural Features of FGF231* - 24 Hours access
EUR €46.00
GBP £40.00
USD $49.00
Rental
This article is also available for rental through DeepDyve.
Citations
Views
Altmetric
Metrics
Total Views 85
61 Pageviews
24 PDF Downloads
Since 2/1/2024
Month: | Total Views: |
---|---|
February 2024 | 17 |
March 2024 | 27 |
April 2024 | 13 |
May 2024 | 23 |
July 2024 | 1 |
August 2024 | 2 |
September 2024 | 2 |
×
Email alerts
Email alerts
Citing articles via
More from Oxford Academic