A diverse range of membrane proteins of Type I or Type II topology also occur as a circulating, soluble form. These soluble forms are often derived from the membrane form by proteolysis by a group of enzymes referred to collectively as ‘secretases‘ or ‘sheddases’. The cleavage generally occurs close to the extracellular face of the membrane, releasing physiologically active protein. This secretion process also provides a mechanism for down-regulating the protein at the cell surface. Examples of such post-translational proteolysis are seen in the Alzheimer's amyloid precursor protein, the vasoregulatory enzyme angiotensin converting enzyme, transforming growth factor-α, the tumour necrosis factor ligand and receptor superfamilies, certain cytokine receptors, and others. Since the proteins concerned are involved in pathophysiological processes such as neurodegeneration, apoptosis, oncogenesis and inflammation, the secretases could provide novel therapeutic targets. Recent characterization of these individual secretases has revealed common features, particularly sensitivity to certain metalloprotease inhibitors and up-regulation of activity by phorbol esters. It is therefore likely that a closely related family of metallosecretases controls the surface expression of multiple integral membrane proteins. Current knowledge of the various secretases are compared in this Review, and strategies for cell-free assays of such proteases are outlined as a prelude to their ultimate purification and cloning.
Skip Nav Destination
Article navigation
January 1997
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
Review Article|
January 15 1997
Membrane protein secretases
Nigel M. HOOPER;
Nigel M. HOOPER
*Department of Biochemistry and Molecular Biology, The University of Leeds, Leeds LS2 9JT, U.K.
Search for other works by this author on:
Eric H. KARRAN;
Eric H. KARRAN
*Department of Biochemistry and Molecular Biology, The University of Leeds, Leeds LS2 9JT, U.K.
†Molecular Neuropathology, SmithKline Beecham Pharmaceuticals, Harlow CM19 5AW, U.K.
Search for other works by this author on:
Anthony J. TURNER
Anthony J. TURNER
‡
*Department of Biochemistry and Molecular Biology, The University of Leeds, Leeds LS2 9JT, U.K.
‡To whom correspondence should be addressed.
Search for other works by this author on:
Publisher: Portland Press Ltd
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1997
1997
Biochem J (1997) 321 (2): 265–279.
Citation
Nigel M. HOOPER, Eric H. KARRAN, Anthony J. TURNER; Membrane protein secretases. Biochem J 15 January 1997; 321 (2): 265–279. doi: https://doi.org/10.1042/bj3210265
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.