TGFbeta induces SIK to negatively regulate type I receptor kinase signaling.

The Journal of Cell Biology
Marcin KowanetzAristidis Moustakas

Abstract

Signal transduction by transforming growth factor beta (TGFbeta) coordinates physiological responses in diverse cell types. TGFbeta signals via type I and type II receptor serine/threonine kinases and intracellular Smad proteins that regulate transcription. Strength and duration of TGFbeta signaling is largely dependent on a negative-feedback program initiated during signal progression. We have identified an inducible gene target of TGFbeta/Smad signaling, the salt-inducible kinase (SIK), which negatively regulates signaling together with Smad7. SIK and Smad7 form a complex and cooperate to down-regulate the activated type I receptor ALK5. We further show that both the kinase and ubiquitin-associated domain of SIK are required for proper ALK5 degradation, with ubiquitin functioning to enhance SIK-mediated receptor degradation. Loss of endogenous SIK results in enhanced gene responses of the fibrotic and cytostatic programs of TGFbeta. We thus identify in SIK a negative regulator that controls TGFbeta receptor turnover and physiological signaling.

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Citations

Jun 7, 2011·Cell and Tissue Research·Carl-Henrik Heldin, Aristidis Moustakas
Jun 28, 2011·Cell and Tissue Research·Yabing MuMaréne Landström
Jan 1, 2013·Pathology Oncology Research : POR·P BaloghA L Kiss
Nov 26, 2008·Cell Research·Peter LönnAristidis Moustakas
Mar 26, 2013·Oncogene·K SavaryA Moustakas
Apr 23, 2011·The Journal of Biological Chemistry·Maria G A HägglundRobert Fredriksson
Oct 27, 2010·The Journal of Biological Chemistry·Anita MorénAristidis Moustakas
Jul 23, 2009·Science Signaling·Hailing ChengJean J Zhao
Mar 17, 2012·Cell & Bioscience·Fei Huang, Ye-Guang Chen
Nov 10, 2015·Expert Opinion on Therapeutic Targets·Wen-Qi DuDong-Sheng Pei
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Aug 4, 2009·Trends in Cell Biology·Jong Seok KangRik Derynck
Feb 25, 2009·Current Opinion in Cell Biology·Carl-Henrik HeldinAristidis Moustakas
Jun 18, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Lingyu LuoDeqiang Huang
Jan 29, 2011·The Biochemical Journal·Xiaohua Yan, Ye-Guang Chen
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Jan 10, 2019·The Journal of Biological Chemistry·Constantinos KolliopoulosLars P van der Heide
Dec 12, 2017·Acta Biochimica Et Biophysica Sinica·Xiaohua YanYe-Guang Chen
Nov 26, 2010·The Journal of Biological Chemistry·Lars P van der HeidePeter ten Dijke
Apr 9, 2009·Acta Biochimica Et Biophysica Sinica·Xiaohua YanYeguang Chen
Aug 3, 2016·Cold Spring Harbor Perspectives in Biology·Carl-Henrik Heldin, Aristidis Moustakas
Jul 28, 2016·Cold Spring Harbor Perspectives in Biology·Akiko Hata, Ye-Guang Chen
Aug 14, 2020·Signal Transduction and Targeted Therapy·Zicheng SunJianping Guo
Feb 22, 2018·Oncotarget·Michael VanlandewijckAristidis Moustakas
Nov 23, 2018·International Journal of Molecular Sciences·Yutaro Tsubakihara, Aristidis Moustakas
Jan 24, 2020·Cell Death & Disease·Luke D HutchinsonGopal P Sapkota
Jul 30, 2014·The Journal of Biological Chemistry·Christopher C PanNam Y Lee
Feb 17, 2021·Journal of Translational Medicine·Jinxiu HuZhimei Lv

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Methods Mentioned

BETA
transfection
immunoprecipitation
ubiquitination

Software Mentioned

Photoshop
Ensembl

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