Gamma-secretase-dependent signaling of receptor tyrosine kinases.

Oncogene
Johannes A M Merilahti, Klaus Elenius

Abstract

Human genome harbors 55 receptor tyrosine kinases (RTK). At least half of the RTKs have been reported to be cleaved by gamma-secretase-mediated regulated intramembrane proteolysis. The two-step process involves releasing the RTK ectodomain to the extracellular space by proteolytic cleavage called shedding, followed by cleavage in the RTK transmembrane domain by the gamma-secretase complex resulting in release of a soluble RTK intracellular domain. This intracellular domain, including the tyrosine kinase domain, can in turn translocate to various cellular compartments, such as the nucleus or proteasome. The soluble intracellular domain may interact with transcriptional regulators and other proteins to induce specific effects on cell survival, proliferation, and differentiation, establishing an additional signaling mode for the cleavable RTKs. On the other hand, the same process can facilitate RTK turnover and proteasomal degradation. In this review we focus on the regulation of RTK shedding and gamma-secretase cleavage, as well as signaling promoted by the soluble RTK ICDs. In addition, therapeutic implications of increased knowledge on RTK cleavage on cancer drug development are discussed.

References

Apr 2, 1999·The European Journal of Neuroscience·E Díaz-RodríguezA Pandiella
Apr 1, 2000·The Journal of Biological Chemistry·C RioG Corfas
Feb 13, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·E RovidaP Dello Sbarba
Feb 14, 2002·Trends in Molecular Medicine·Esther ZwickAxel Ullrich
Jan 22, 2004·Biochemical and Biophysical Research Communications·Chen Lai, Linyin Feng
Feb 19, 2004·The Journal of Biological Chemistry·Daniel V BaxMartin J Humphries
Jul 2, 2004·The EMBO Journal·Kristi G BacheHarald Stenmark
Aug 24, 2004·The Journal of Biological Chemistry·Kulandaivelu S VetrivelGopal Thinakaran
Nov 10, 2004·The Journal of Cell Biology·Christopher C WilliamsFrank E Jones
Feb 18, 2005·Journal of Lipid Research·Yasuomi UranoTatsuhiko Kodama
Mar 1, 2005·Cancer Research·Teemu T JunttilaKlaus Elenius
Mar 5, 2005·The Journal of Biological Chemistry·Gregory A VidalFrank E Jones
Jun 30, 2005·The Journal of Biological Chemistry·Rajeswara Rao Arasada, Graham Carpenter
Jul 4, 2006·The Journal of Biological Chemistry·Bryan Linggi, Graham Carpenter
Jul 14, 2006·Molecular Biology of the Cell·Rebecca S Muraoka-CookH Shelton Earp
Apr 13, 2007·The Journal of Biological Chemistry·Claudia LitterstNikolaos K Robakis
May 26, 2007·Biochemical and Biophysical Research Communications·Brian McElroyJustin V McCarthy
Jun 20, 2007·Biochemical and Biophysical Research Communications·K KasugaT Ikeuchi
Aug 31, 2007·The Journal of Biological Chemistry·Marie B MarronNicholas P J Brindle
Jun 10, 2008·The Journal of Biological Chemistry·Pamela OsenkowskiDennis J Selkoe
Oct 9, 2008·Seminars in Cell & Developmental Biology·Gillian Murphy
Oct 24, 2008·PLoS Biology·Matthew L HemmingDennis J Selkoe
Nov 14, 2008·Nature Reviews. Cancer·Gillian Murphy
Mar 20, 2009·Molecular Biology of the Cell·Bénédicte FoveauDavid Tulasne

❮ Previous
Next ❯

Citations

Sep 13, 2019·Critical Reviews in Clinical Laboratory Sciences·Fatemeh MoosaviOmidreza Firuzi
Dec 24, 2018·Journal of Clinical Medicine·Natalia PorębskaŁukasz Opaliński
May 2, 2020·Life Science Alliance·Esteban GutierrezJochen Walter
Jun 21, 2020·The Journal of Biological Chemistry·Veera K OjalaKlaus Elenius
Nov 1, 2020·International Journal of Molecular Sciences·Yves Combarnous, Thi Mong Diep Nguyen
Jan 1, 2021·Frontiers in Cardiovascular Medicine·Alkmini A Papadopoulou, Regina Fluhrer
Dec 17, 2020·Molecular Cancer Therapeutics·Marika K A KoivuKlaus Elenius
May 20, 2020·Seminars in Cell & Developmental Biology·Manuel HitzenbergerChristina Scharnagl
Jul 1, 2020·Trends in Molecular Medicine·Dirk Schmidt-Arras, Frank-D Böhmer
May 6, 2021·Biomolecules·Hao Huang
Jun 3, 2021·International Journal of Molecular Sciences·Francesca TosettiMaria Raffaella Zocchi
Dec 25, 2021·The FEBS Journal·Hiba-Tun-Noor Afshan MahmoodAthina-Myrto Chioni

❮ Previous
Next ❯

Methods Mentioned

BETA
RIP
glycosylation
ubiquitination

Related Concepts

Related Feeds

Cell Signaling by Tyrosine Kinases

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. RTKs have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Discover the latest research on cell signaling and RTK here.

© 2022 Meta ULC. All rights reserved