The TNF receptor, RELT, binds SPAK and uses it to mediate p38 and JNK activation

Biochemical and Biophysical Research Communications
Tara C PolekTaly Spivak-Kroizman

Abstract

Receptor expressed in lymphoid tissues (RELT) is a new member of the TNFR family with little known regarding its signaling. Typically, TNFRs engage TRAFs for activation of NF-kappaB and MAPK cascades. We found that RELT does not use the standard signaling pathways characteristic of other TNFRs. While overexpression of RELT in 293 cells induced p38 and JNK activation, it did not activate NF-kappaB. In addition, no binding of RELT to TRAF1,2,3,5, or 6 was detected. Using a yeast two-hybrid system, we identified a Ste20-related proline-alanine-rich kinase (SPAK) that binds RELT. Disruption of the SPAK binding motif, 349RFRV, in RELT inhibited RELT activation of p38 and JNK. In addition, a kinase-dead SPAK acted as an inhibitor of RELT signaling. Thus, we conclude that RELT does not rely on the canonical TRAF pathways for its function, but instead uses a kinase, SPAK, to mediate p38 and JNK activation.

References

Dec 22, 1999·Oncogene·L A Sabourin, M A Rudnicki
Sep 12, 2000·Oncogene·A M JohnstonH J DeAizpurua
Apr 24, 2001·Trends in Cell Biology·I DanA Kusumi
Oct 19, 2001·Oncogene·J R Bradley, J S Pober
Feb 14, 2002·Trends in Biochemical Sciences·Jean-Luc BodmerJürg Tschopp
May 13, 2003·The Journal of Biological Chemistry·Brian F X Dowd, Biff Forbush
Sep 2, 2003·Nature Reviews. Immunology·Bharat B Aggarwal
Oct 14, 2003·Biochemical Pharmacology·Upasna Gaur, Bharat B Aggarwal
Nov 7, 2003·Journal of Clinical Immunology·Anjana Bhardwaj, Bharat B Aggarwal
Jan 7, 2004·The Journal of Biological Chemistry·Wei ChenMelanie H Cobb
May 26, 2004·Biochemical Society Transactions·P M de Souza, M A Lindsay

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Citations

Sep 11, 2012·Cellular & Molecular Immunology·Hailei YinZhaocai Zhou
Dec 29, 2011·Journal of Allergy·Steven R White
Jan 23, 2010·Cellular and Molecular Life Sciences : CMLS·Sónia Moniz, Peter Jordan
Sep 1, 2009·The American Journal of Pathology·Cynthia E BalatoniMichael A Teitell
Sep 5, 2006·Biochemical and Biophysical Research Communications·Tara C PolekTaly R Spivak-Kroizman
Dec 9, 2009·Cellular Immunology·John K CusickMary E Reyland
Mar 19, 2013·The American Journal of Pathology·Yuchen ZhangYutao Yan
Oct 23, 2016·Free Radical Biology & Medicine·Tsai-Jung LinShuk-Man Ka
Aug 24, 2018·European Journal of Immunology·Beom K ChoiByoung S Kwon
Oct 18, 2012·Physiological Reviews·Kenneth B Gagnon, Eric Delpire
Oct 13, 2006·Physiological Genomics·Eric Delpire, Kenneth B E Gagnon
Nov 5, 2011·Molecular and Cellular Biochemistry·John K CusickMary E Reyland
Jun 11, 2019·Oxidative Medicine and Cellular Longevity·Shicheng BiSonghua Hu
Mar 11, 2020·Nature Reviews. Neurology·Jason K KarimyKristopher T Kahle
Jun 25, 2021·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·Stephanie M RobertKristopher T Kahle

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