NDLI: Insulin stimulates the cleavage and release of the extracellular domain of Klotho by ADAM10 and ADAM17

Content Provider	PubMed Central
Author	Chen, Ci-di Podvin, Sonia Gillespie, Earl Leeman, Susan E. Abraham, Carmela R.
Copyright Year	2007
Abstract	Cleavage and release (shedding) of membrane proteins is a critical regulatory step in many normal and pathological processes. Evidence suggests that the antiaging transmembrane protein Klotho (KL) is shed from the cell surface by proteolytic cleavage. In this study, we attempted to identify the enzymes responsible for the shedding of KL by treating KL-transfected COS-7 cells with a panel of proteinase inhibitors and measuring cleavage products by Western blot. We report that metalloproteinase inhibitors, including EDTA, EGTA, and TAPI-1, inhibit the shedding of KL, whereas insulin increases shedding. The effects of the inhibitors in KL-transfected COS-7 cells were repeated in studies on rat kidney slices ex vivo, which validates the use of COS-7 cells as our model system. Tissue inhibitor of metalloproteinase (Timp)-3 effectively inhibits KL cleavage, whereas Timp-1 and Timp-2 do not, a profile that indicates the involvement of members of the A Desintegrin and Metalloproteinase (ADAM) family. Cotransfection of KL with either ADAM10 or ADAM17 enhances KL cleavage, whereas cotransfection of KL with small interference RNAs specific to ADAM10 and ADAM17 inhibits KL secretion. These results indicate that KL shedding is mediated mainly by ADAM10 and ADAM17 in KL-transfected COS-7 cells. The effect of insulin is abolished when ADAM10 or ADAM17 are silenced. Furthermore, we demonstrate that the effect of insulin on KL shedding is inhibited by wortmannin, showing that insulin acts through a PI3K-dependent pathway. Insulin enhances KL shedding without increasing ADAM10 and ADAM17 mRNA and protein levels, suggesting that it acts by stimulating their proteolytic activities.
Related Links	http://dx.doi.org/10.1073/pnas.0709805104
Starting Page	19796
File Format	PDF
ISSN	10916490
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	50
Volume Number	104
Language	English
Publisher	National Academy of Sciences
Publisher Date	2007-12-11
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Insulin stimulates the cleavage and release of the extracellular domain of Klotho by ADAM10 and ADAM17.

Cleavage Site Localization Differentially Controls Interleukin-6 Receptor Proteolysis by ADAM10 and ADAM17

Cleavage Site Localization Differentially Controls Interleukin-6 Receptor Proteolysis by ADAM10 and ADAM17

Binding of platelet glycoprotein Ibα to von Willebrand factor domain A1 stimulates the cleavage of the adjacent domain A2 by ADAMTS13

N-Terminal Cleavage and Release of the Ectodomain of Flt1 Is Mediated via ADAM10 and ADAM 17 and Regulated by VEGFR2 and the Flt1 Intracellular Domain

CHOLESTEROL EFFLUX STIMULATES METALLOPROTEINASE MEDIATED CLEAVAGE OF OCCLUDIN AND RELEASE OF EXTRACELLULAR MEMBRANE PARTICLES CONTAINING ITS C-TERMINAL FRAGMENTS

The Fas ligand intracellular domain is released by ADAM10 and SPPL2a cleavage in T-cells

ADAM10 and ADAM17: New Players in Trastuzumab Resistance

Initial site of insulin cleavage by insulin protease.

Insulin stimulates the cleavage and release of the extracellular domain of Klotho by ADAM10 and ADAM17

Similar Documents

Insulin stimulates the cleavage and release of the extracellular domain of Klotho by ADAM10 and ADAM17.

Cleavage Site Localization Differentially Controls Interleukin-6 Receptor Proteolysis by ADAM10 and ADAM17

Cleavage Site Localization Differentially Controls Interleukin-6 Receptor Proteolysis by ADAM10 and ADAM17

Binding of platelet glycoprotein Ibα to von Willebrand factor domain A1 stimulates the cleavage of the adjacent domain A2 by ADAMTS13

N-Terminal Cleavage and Release of the Ectodomain of Flt1 Is Mediated via ADAM10 and ADAM 17 and Regulated by VEGFR2 and the Flt1 Intracellular Domain

CHOLESTEROL EFFLUX STIMULATES METALLOPROTEINASE MEDIATED CLEAVAGE OF OCCLUDIN AND RELEASE OF EXTRACELLULAR MEMBRANE PARTICLES CONTAINING ITS C-TERMINAL FRAGMENTS

The Fas ligand intracellular domain is released by ADAM10 and SPPL2a cleavage in T-cells

ADAM10 and ADAM17: New Players in Trastuzumab Resistance

Initial site of insulin cleavage by insulin protease.

Insulin stimulates the cleavage and release of the extracellular domain of Klotho by ADAM10 and ADAM17