The tuberous sclerosis complex subunit TBC1D7 is stabilized by Akt phosphorylation-mediated 14-3-3 binding.

The Journal of Biological Chemistry
James P MadiganYufeng Tong

Abstract

The tuberous sclerosis complex (TSC) is a negative regulator of mTOR complex 1, a signaling node promoting cellular growth in response to various nutrients and growth factors. However, several regulators in TSC signaling still await discovery and characterization. Using pulldown and MS approaches, here we identified the TSC complex member, TBC1 domain family member 7 (TBC1D7), as a binding partner for PH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1), a negative regulator of Akt kinase signaling. Most TBC domain-containing proteins function as Rab GTPase-activating proteins (RabGAPs), but the crystal structure of TBC1D7 revealed that it lacks residues critical for RabGAP activity. Sequence analysis identified a putative site for both Akt-mediated phosphorylation and 14-3-3 binding at Ser-124, and we found that Akt phosphorylates TBC1D7 at Ser-124. However, this phosphorylation had no effect on the binding of TBC1D7 to TSC1, but stabilized TBC1D7. Moreover, 14-3-3 protein both bound and stabilized TBC1D7 in a growth factor-dependent manner, and a phospho-deficient substitution, S124A, prevented this interaction. The crystal structure of 14-3-3ζ in complex with a phospho-Ser-124 TBC1D7 peptide confirmed the direct ...Continue Reading

References

Oct 29, 2000·Acta Crystallographica. Section D, Biological Crystallography·L M RiceA T Brunger
Sep 28, 2002·Acta Crystallographica. Section D, Biological Crystallography·Thomas R Schneider, George M Sheldrick
Apr 22, 2003·Proceedings of the National Academy of Sciences of the United States of America·Carolyn R HoyalBernard M Babior
Jun 26, 2003·Nucleic Acids Research·John C ObenauerMichael B Yaffe
Nov 11, 2003·Trends in Biochemical Sciences·Brendan D Manning, Lewis C Cantley
Dec 4, 2003·Journal of Synchrotron Radiation·Thomas Terwilliger
May 29, 2004·The Journal of Biological Chemistry·Xiaofang LiHung-Ying Kao
Jan 1, 1996·Acta Crystallographica. Section D, Biological Crystallography·J P Abrahams, A G Leslie
May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Dec 2, 2004·Biochimica Et Biophysica Acta·Andrew R WillemsMike Tyers
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
May 9, 2006·Seminars in Cancer Biology·Alastair Aitken
Jul 21, 2006·Acta Crystallographica. Section D, Biological Crystallography·Wladek MinorMaksymilian Chruszcz
Aug 2, 2006·The Biochemical Journal·Sarah H ConnerDaan M F Van Aalten
Aug 25, 2006·Acta Crystallographica. Section D, Biological Crystallography·Kevin Cowtan
Dec 14, 2006·Acta Crystallographica. Section D, Biological Crystallography·Airlie J McCoy
Dec 19, 2006·Methods in Molecular Biology·Clemens VonrheinGérard Bricogne
Jan 4, 2007·The Journal of Biological Chemistry·Géraldine RocherFrançoise Porteu
Feb 9, 2007·The Journal of Biological Chemistry·Dexing FangZhimin Lu
Apr 5, 2007·Nature Protocols·Andrej ShevchenkoMatthias Mann
Jul 3, 2007·Cell·Brendan D Manning, Lewis C Cantley
Jul 25, 2007·The Journal of Cell Biology·Shin-Ichiro YoshimuraFrancis A Barr
Jul 31, 2007·Biochemical and Biophysical Research Communications·Akio NakashimaKazuyoshi Yonezawa
Feb 22, 2008·Nucleic Acids Research·Jimin PeiNick V Grishin
Mar 22, 2008·The Journal of Biological Chemistry·Vanessa Lopez-PajaresZhi-Min Yuan
May 8, 2008·Nucleic Acids Research·Roberto Mosca, Thomas R Schneider
May 27, 2008·Nature Reviews. Cancer·David Frescas, Michele Pagano
Aug 30, 2008·Lancet·Paolo CuratoloSergiusz Jozwiak
Jun 6, 2009·Annual Review of Biochemistry·Raymond J Deshaies, Claudio A P Joazeiro
Jun 6, 2009·Annual Review of Biochemistry·Daniel Finley
Nov 20, 2009·Cell Cycle·Chong XuBarry M Gumbiner
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
May 12, 2010·Nucleic Acids Research·Liisa Holm, Päivi Rosenström
Jun 2, 2010·Molecular Cell·Meng QiaoArthur B Pardee

❮ Previous
Next ❯

Citations

Jun 9, 2020·Proteomics·Tianyu F QiYinsheng Wang
Oct 3, 2020·Molecular Cancer·Tianshui SunQing Yang
May 18, 2021·Biochemistry. Biokhimii︠a︡·Irina S BokshaGulnur Sh Burbaeva

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.