Plasminogen activator inhibitor 1 is an intracellular inhibitor of furin proprotein convertase

• Published in: Journal of cell science Vol. 124; no. Pt 8; pp. 1224 - 1230
• Main Authors: Bernot, Denis, Stalin, Jimmy, Stocker, Pierre, Bonardo, Bernadette, Scroyen, Ilse, Alessi, Marie-Christine, Peiretti, Franck
• Format: Journal Article
• Language: English
• Published: England Company of Biologists 15.04.2011
• Subjects: Cell Line; Chemical Sciences; Enzyme Inhibitors - metabolism; Furin - antagonists & inhibitors; Furin - genetics; Furin - metabolism; Golgi Apparatus - enzymology; Golgi Apparatus - metabolism; Humans; Intracellular Space - enzymology; Intracellular Space - genetics; Intracellular Space - metabolism; Plasminogen Activator Inhibitor 1 - genetics; Plasminogen Activator Inhibitor 1 - metabolism; Protein Binding; Protein Processing, Post-Translational
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.079889

Proprotein convertases (PCs) are a family of serine proteases that are involved in the post-translational processing and activation of a wide range of regulatory proteins. The upstream role of PCs in the control of many physiological and pathological processes generates a growing interest in understanding their regulation. Here, we demonstrate that the serine protease inhibitor plasminogen activator inhibitor 1 (PAI-1) forms an SDS-stable complex with the PC furin, which leads to the inhibition of the intra-Golgi activity of furin. It is known that elevated PAI-1 plasma levels are correlated with the occurrence of the metabolic syndrome and type 2 diabetes, and we show that PAI-1 reduces the furin-dependent maturation and activity of the insulin receptor and ADAM17: two proteins involved in the onset of these metabolic disorders. In addition to demonstrating that PAI-1 is an intracellular inhibitor of furin, this study also provides arguments in favor of an active role for PAI-1 in the development of metabolic disorders.