Competition between members of the tribbles pseudokinase protein family shapes their interactions with mitogen activated protein kinase pathways.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Mitogen-Activated Protein Kinases/*metabolism ; Protein Serine-Threonine Kinases/*metabolism; Animals ; Binding, Competitive ; Enzyme Activators/metabolism ; Humans ; Mitogen-Activated Protein Kinases/antagonists & inhibitors ; Signal Transduction ; Subcellular Fractions/enzymology

Spatio-temporal regulation of intracellular signalling networks is key to normal cellular physiology; dysregulation of which leads to disease. The family of three mammalian tribbles proteins has emerged as an important controller of signalling via regulating the activity of mitogen activated protein kinases (MAPK), the PI3-kinase induced signalling network and E3 ubiquitin ligases. However, the importance of potential redundancy in the action of tribbles and how the differences in affinities for the various binding partners may influence signalling control is currently unclear. We report that tribbles proteins can bind to an overlapping set of MAPK-kinases (MAPKK) in live cells and dictate the localisation of the complexes. Binding studies in transfected cells reveal common regulatory mechanisms and suggest that tribbles and MAPKs may interact with MAPKKs in a competitive manner. Computational modelling of the impact of tribbles on MAPK activation suggests a high sensitivity of this system to changes in tribbles levels, highlighting that these proteins are ideally placed to control the dynamics and balance of activation of concurrent signalling pathways.

Biochem Soc Trans. 2015 Oct;43(5):1112-5. (PMID: 26517933)
Nat Chem Biol. 2006 Jun;2(6):329-37. (PMID: 16680159)
Cell Mol Life Sci. 2006 Jul;63(14):1632-41. (PMID: 16715410)
Mol Cell Oncol. 2015 Apr 18;2(3):e980134. (PMID: 27308456)
Cell Signal. 2008 May;20(5):942-8. (PMID: 18276110)
Blood. 2010 Oct 14;116(15):2768-75. (PMID: 20610816)
J Am Soc Nephrol. 2008 Jun;19(6):1116-27. (PMID: 18369086)
J Immunol Res. 2014;2014:240396. (PMID: 25133193)
Nat Commun. 2015 Aug 13;6:7951. (PMID: 26268733)
Science. 2006 Jun 23;312(5781):1763-6. (PMID: 16794074)
J Biol Chem. 2007 Aug 17;282(33):24075-82. (PMID: 17576771)
Immunol Lett. 2006 Apr 15;104(1-2):171-7. (PMID: 16364454)
Inflamm Bowel Dis. 2012 May;18(5):877-88. (PMID: 22271508)
Curr Mol Med. 2013 Jan;13(1):80-5. (PMID: 22834837)
Blood. 2013 May 23;121(21):4265-70. (PMID: 23550039)
Nat Cell Biol. 2004 Apr;6(4):358-65. (PMID: 15048128)
Methods Mol Biol. 2004;261:411-26. (PMID: 15064473)
Cell Signal. 2006 Feb;18(2):202-14. (PMID: 15990277)
J Biol Chem. 2007 Jun 22;282(25):18379-87. (PMID: 17452330)
PLoS One. 2016 May 31;11(5):e0156139. (PMID: 27243235)
Blood. 2012 Mar 15;119(11):2608-11. (PMID: 22294728)
Curr Opin Lipidol. 2012 Apr;23(2):122-6. (PMID: 22274752)
Biochem Soc Trans. 2013 Aug;41(4):1096-100. (PMID: 23863185)
Biochem Soc Trans. 2005 Dec;33(Pt 6):1405-6. (PMID: 16246130)
J Cell Physiol. 2003 Sep;196(3):419-29. (PMID: 12891699)
Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10078-83. (PMID: 8816754)
Structure. 2016 May 3;24(5):687-96. (PMID: 27041596)
Cell Death Differ. 2015 Jan;22(1):131-44. (PMID: 25168244)
J Biol Chem. 1999 Dec 31;274(53):37941-9. (PMID: 10608861)
J Biol Chem. 1994 Aug 5;269(31):19947-52. (PMID: 8051079)
Biochem Soc Trans. 2015 Oct;43(5):1069-74. (PMID: 26517925)
J Biol Chem. 2003 Aug 15;278(33):30881-8. (PMID: 12663663)
Science. 1998 May 8;280(5365):895-8. (PMID: 9572732)
FEBS Lett. 2014 Nov 28;588(23 ):4334-41. (PMID: 25311538)
Cell Signal. 2007 Feb;19(2):238-50. (PMID: 16963228)
J Biol Chem. 2004 Oct 8;279(41):42703-8. (PMID: 15299019)
Structure. 2015 Nov 3;23(11):2111-21. (PMID: 26455797)
J Exp Med. 2007 Sep 3;204(9):2233-9. (PMID: 17724128)
Immunol Lett. 2010 May 4;130(1-2):115-24. (PMID: 20005259)
Blood. 2010 Aug 26;116(8):1321-8. (PMID: 20410507)
Int Immunol. 2008 Dec;20(12):1543-50. (PMID: 18952906)
Biochem Soc Trans. 2011 Apr;39(2):684-7. (PMID: 21428962)
Science. 2003 Jun 6;300(5625):1574-7. (PMID: 12791994)
Biochem Biophys Res Commun. 2010 Feb 12;392(3):289-94. (PMID: 20064487)
Eur J Biochem. 1997 Sep 15;248(3):660-8. (PMID: 9342215)
Biochem J. 2015 Apr 1;467(1):47-62. (PMID: 25583260)
Scientifica (Cairo). 2013;2013:750871. (PMID: 24490110)
Mol Cell Biol. 1999 Feb;19(2):1569-81. (PMID: 9891090)
Biochem Soc Trans. 2015 Oct;43(5):1085-8. (PMID: 26517928)

PG/05/100 United Kingdom British Heart Foundation; BB/F016840/1 United Kingdom Biotechnology and Biological Sciences Research Council

0 (Enzyme Activators)
EC 2.7.11.1 (Protein Serine-Threonine Kinases)
EC 2.7.11.24 (Mitogen-Activated Protein Kinases)

Date Created: 20160908 Date Completed: 20180614 Latest Revision: 20211204

20250114

PMC5013389

10.1038/srep32667

27600771