Caveolin-1-dependent activation of the metalloprotease TACE/ADAM17 by TGF-β in hepatocytes requires activation of Src and the NADPH oxidase NOX1

The FEBS Journal
J Moreno-CàceresIsabel Fabregat

Abstract

Transforming growth factor-β (TGF-β) plays a dual role in hepatocytes, inducing both pro- and anti-apoptotic responses, the balance between which decides cell fate. Survival signals are mediated by the epidermal growth factor receptor (EGFR) pathway, which is activated by TGF-β. We have previously shown that caveolin-1 (CAV1) is required for activation of the metalloprotease tumour necrosis factor (TNF)-α-converting enzyme/a disintegrin and metalloproteinase 17 (TACE/ADAM17), and hence transactivation of the EGFR pathway. The specific mechanism by which TACE/ADAM17 is activated has not yet been determined. Here we show that TGF-β induces phosphorylation of sarcoma kinase (Src) in hepatocytes, a process that is impaired in Cav1(-/-) hepatocytes, coincident with a decrease in phosphorylated Src in detergent-resistant membrane fractions. TGF-β-induced activation of TACE/ADAM17 and EGFR phosphorylation were blocked using the Src inhibitor PP2. Cav1(+/+) hepatocytes showed early production of reactive oxygen species (ROS) induced by TGF-β, which was not seen in Cav1(-/-) cells. Production of ROS was inhibited by both the NADPH oxidase 1 (NOX1) inhibitor STK301831 and NOX1 knock-down, which also impaired TACE/ADAM17 activation and th...Continue Reading

References

Aug 28, 2003·Diabetes·Angela M ValverdeManuel Benito
Dec 13, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Lula L HilenskiKathy K Griendling
Jan 15, 2004·Experimental Cell Research·Francisco ValdésIsabel Fabregat
Jun 23, 2004·Oncogene·Seok Soon ParkKyeong Sook Choi
Oct 11, 2008·Journal of Hepatology·Irene Carmona-CuencaIsabel Fabregat
Nov 13, 2008·Antioxidants & Redox Signaling·Masuko Ushio-Fukai
Jul 25, 2009·Free Radical Biology & Medicine·David I Brown, Kathy K Griendling
Oct 23, 2009·Molecular Biology of the Cell·Timothy J MyersSusan Wohler Sunnarborg
Dec 8, 2009·The Journal of Biological Chemistry·Rafael MayoralPaloma Martín-Sanz
Dec 28, 2010·Journal of Hepatology·Christoph MeyerSteven Dooley
Jan 19, 2013·Cell Death & Disease·C MeyerS Dooley
Mar 7, 2013·The FEBS Journal·Aoife Corcoran, Thomas G Cotter
May 4, 2013·Critical Reviews in Biochemistry and Molecular Biology·Thu H Truong, Kate S Carroll
May 4, 2013·American Journal of Physiology. Gastrointestinal and Liver Physiology·Netanya Y SpencerJohn F Engelhardt
Feb 1, 2014·Biochimica Et Biophysica Acta·Anita Hryniewicz-JankowskaAleksander F Sikorski
Jan 15, 2015·Archives of Biochemistry and Biophysics·Hongqiao ZhangHenry Jay Forman

❮ Previous
Next ❯

Citations

Oct 13, 2016·Scientific Reports·Inken LorenzenStefan Düsterhöft
Apr 28, 2018·International Journal of Molecular Sciences·Laia CajaIsabel Fabregat
Nov 10, 2017·Oxidative Medicine and Cellular Longevity·Inken LorenzenEva-Maria Hanschmann
Sep 27, 2018·Frontiers in Oncology·Isabel Fabregat, Daniel Caballero-Díaz
Dec 20, 2020·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Kegui ZhangXiaohua Yan
Feb 13, 2021·Cellular and Molecular Life Sciences : CMLS·Tatsuo KawaiSatoru Eguchi
Jun 3, 2021·International Journal of Molecular Sciences·Andy RuizLeslie Chavez-Galan

❮ Previous
Next ❯

Related Concepts

Related Feeds

Caveolins & Signal Transduction

Caveolins are small proteins with a hairpin loop conformation that are located in the plasma membrane of various cell types where they bind cholesterol and interact with receptors essential for several signal transduction pathways. Here is the latest research.