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Hydrogen peroxide-dependent oxidation of ERK2 within its D-recruitment site alters its substrate selection.
Postiglione, Anthony E; Adams, Laquaundra L; Ekhator, Ese S; Odelade, Anuoluwapo E; Patwardhan, Supriya; Chaudhari, Meenal; Pardue, Avery S; Kumari, Anjali; LeFever, William A; Tornow, Olivia P; Kaoud, Tamer S; Neiswinger, Johnathan; Jeong, Jun Seop; Parsonage, Derek; Nelson, Kimberly J; Kc, Dukka B; Furdui, Cristina M; Zhu, Heng; Wommack, Andrew J; Dalby, Kevin N; Dong, Ming; Poole, Leslie B; Keyes, Jeremiah D; Newman, Robert H.
Afiliación
  • Postiglione AE; Department of Biology, North Carolina A&T State University, Greensboro, NC 27411, USA.
  • Adams LL; Department of Biology, Wake Forest University, Winston-Salem, NC 27101, USA.
  • Ekhator ES; Department of Biology, North Carolina A&T State University, Greensboro, NC 27411, USA.
  • Odelade AE; Department of Biology, North Carolina A&T State University, Greensboro, NC 27411, USA.
  • Patwardhan S; Department of Biology, North Carolina A&T State University, Greensboro, NC 27411, USA.
  • Chaudhari M; Department of Biology, North Carolina A&T State University, Greensboro, NC 27411, USA.
  • Pardue AS; Department of Biology, North Carolina A&T State University, Greensboro, NC 27411, USA.
  • Kumari A; Department of Computational Data Science and Engineering, North Carolina A&T State University, Greensboro, NC 27411, USA.
  • LeFever WA; Department of Mathematics and Computer Science, University of Virginia at Wise, Wise, VA 24293, USA.
  • Tornow OP; Department of Biology, North Carolina A&T State University, Greensboro, NC 27411, USA.
  • Kaoud TS; Department of Biology, North Carolina A&T State University, Greensboro, NC 27411, USA.
  • Neiswinger J; Department of Chemistry, High Point University, High Point, NC 27268, USA.
  • Jeong JS; Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
  • Parsonage D; Department of Chemistry, High Point University, High Point, NC 27268, USA.
  • Nelson KJ; Division of Chemical Biology and Medicinal Chemistry, The University of Texas at Austin, Austin, TX 78712, USA.
  • Kc DB; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Furdui CM; Department of Biology, Belhaven University, Jackson, MS 39202, USA.
  • Zhu H; Department of Biology, North Carolina A&T State University, Greensboro, NC 27411, USA.
  • Wommack AJ; Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
  • Dalby KN; Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
  • Dong M; Department of Computer Science, Michigan Technological University, Houghton, MI 49931, USA.
  • Poole LB; Department of Internal Medicine, Section on Molecular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
  • Keyes JD; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Newman RH; Department of Chemistry, High Point University, High Point, NC 27268, USA.
iScience ; 26(10): 107817, 2023 Oct 20.
Article en En | MEDLINE | ID: mdl-37744034
Extracellular signal-regulated kinases 1 and 2 (ERK1/2) are dysregulated in many pervasive diseases. Recently, we discovered that ERK1/2 is oxidized by signal-generated hydrogen peroxide in various cell types. Since the putative sites of oxidation lie within or near ERK1/2's ligand-binding surfaces, we investigated how oxidation of ERK2 regulates interactions with the model substrates Sub-D and Sub-F. These studies revealed that ERK2 undergoes sulfenylation at C159 on its D-recruitment site surface and that this modification modulates ERK2 activity differentially between substrates. Integrated biochemical, computational, and mutational analyses suggest a plausible mechanism for peroxide-dependent changes in ERK2-substrate interactions. Interestingly, oxidation decreased ERK2's affinity for some D-site ligands while increasing its affinity for others. Finally, oxidation by signal-generated peroxide enhanced ERK1/2's ability to phosphorylate ribosomal S6 kinase A1 (RSK1) in HeLa cells. Together, these studies lay the foundation for examining crosstalk between redox- and phosphorylation-dependent signaling at the level of kinase-substrate selection.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: IScience Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: IScience Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos