دورية أكاديمية
أعرض في EDS

A respiratory chain controlled signal transduction cascade in the mitochondrial intermembrane space mediates hydrogen peroxide signaling.

التفاصيل البيبلوغرافية
العنوان: A respiratory chain controlled signal transduction cascade in the mitochondrial intermembrane space mediates hydrogen peroxide signaling.
المؤلفون: Patterson HC; Whitehead Institute for Biomedical Research, Cambridge, MA 02142; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115; Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, Cambridge, MA 02139; Institut fuer Klinische Chemie und Biochemie, Klinikum rechts der Isar, 81675 Munich, Germany; ckunst@partners.org lodish@wi.mit.edu., Gerbeth C; Institute for Biochemistry and Molecular Biology and BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany;, Thiru P; Whitehead Institute for Biomedical Research, Cambridge, MA 02142;, Vögtle NF; Institute for Biochemistry and Molecular Biology and BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany;, Knoll M; Whitehead Institute for Biomedical Research, Cambridge, MA 02142;, Shahsafaei A; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115;, Samocha KE; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114; Broad Institute, Cambridge, MA 02142;, Huang CX; Whitehead Institute for Biomedical Research, Cambridge, MA 02142;, Harden MM; Whitehead Institute for Biomedical Research, Cambridge, MA 02142;, Song R; Whitehead Institute for Biomedical Research, Cambridge, MA 02142;, Chen C; Whitehead Institute for Biomedical Research, Cambridge, MA 02142;, Kao J; Whitehead Institute for Biomedical Research, Cambridge, MA 02142;, Shi J; Whitehead Institute for Biomedical Research, Cambridge, MA 02142;, Salmon W; Whitehead Institute for Biomedical Research, Cambridge, MA 02142;, Shaul YD; Whitehead Institute for Biomedical Research, Cambridge, MA 02142;, Stokes MP; Cell Signaling Technology, Danvers, MA 01923;, Silva JC; Cell Signaling Technology, Danvers, MA 01923;, Bell GW; Whitehead Institute for Biomedical Research, Cambridge, MA 02142;, MacArthur DG; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114; Broad Institute, Cambridge, MA 02142;, Ruland J; Institut fuer Klinische Chemie und Biochemie, Klinikum rechts der Isar, 81675 Munich, Germany;, Meisinger C; Institute for Biochemistry and Molecular Biology and BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany;, Lodish HF; Whitehead Institute for Biomedical Research, Cambridge, MA 02142; Departments of Biology and Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142 ckunst@partners.org lodish@wi.mit.edu.
المصدر: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2015 Oct 20; Vol. 112 (42), pp. E5679-88. Date of Electronic Publication: 2015 Oct 05.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : National Academy of Sciences
مواضيع طبية MeSH: Electron Transport* , Signal Transduction*, Hydrogen Peroxide/*metabolism , Mitochondrial Membranes/*metabolism, Animals ; Cells, Cultured ; Chickens ; Enzyme Activation ; Intracellular Signaling Peptides and Proteins/metabolism ; Mice ; Phosphorylation ; Protein-Tyrosine Kinases/metabolism ; Reactive Oxygen Species/metabolism ; Syk Kinase ; Tyrosine/metabolism
مستخلص: Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) govern cellular homeostasis by inducing signaling. H2O2 modulates the activity of phosphatases and many other signaling molecules through oxidation of critical cysteine residues, which led to the notion that initiation of ROS signaling is broad and nonspecific, and thus fundamentally distinct from other signaling pathways. Here, we report that H2O2 signaling bears hallmarks of a regular signal transduction cascade. It is controlled by hierarchical signaling events resulting in a focused response as the results place the mitochondrial respiratory chain upstream of tyrosine-protein kinase Lyn, Lyn upstream of tyrosine-protein kinase SYK (Syk), and Syk upstream of numerous targets involved in signaling, transcription, translation, metabolism, and cell cycle regulation. The active mediators of H2O2 signaling colocalize as H2O2 induces mitochondria-associated Lyn and Syk phosphorylation, and a pool of Lyn and Syk reside in the mitochondrial intermembrane space. Finally, the same intermediaries control the signaling response in tissues and species responsive to H2O2 as the respiratory chain, Lyn, and Syk were similarly required for H2O2 signaling in mouse B cells, fibroblasts, and chicken DT40 B cells. Consistent with a broad role, the Syk pathway is coexpressed across tissues, is of early metazoan origin, and displays evidence of evolutionary constraint in the human. These results suggest that H2O2 signaling is under control of a signal transduction pathway that links the respiratory chain to the mitochondrial intermembrane space-localized, ubiquitous, and ancient Syk pathway in hematopoietic and nonhematopoietic cells.
التعليقات: Erratum in: Proc Natl Acad Sci U S A. 2016 Apr 5;113(14):E2094. (PMID: 27036011)
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معلومات مُعتمدة: 5 P30 CA06516 United States CA NCI NIH HHS; T32 HL007627 United States HL NHLBI NIH HHS; K08 GM102718 United States GM NIGMS NIH HHS; KO8 GM102718 United States GM NIGMS NIH HHS; P30 CA006516 United States CA NCI NIH HHS; R01 DK047618 United States DK NIDDK NIH HHS
فهرسة مساهمة: Keywords: Btk; PTPN6; dasatinib; fostamatinib; rotenone
المشرفين على المادة: 0 (Intracellular Signaling Peptides and Proteins)
0 (Reactive Oxygen Species)
42HK56048U (Tyrosine)
BBX060AN9V (Hydrogen Peroxide)
EC 2.7.10.1 (Protein-Tyrosine Kinases)
EC 2.7.10.2 (SYK protein, human)
EC 2.7.10.2 (Syk Kinase)
EC 2.7.10.2 (Syk protein, mouse)
تواريخ الأحداث: Date Created: 20151007 Date Completed: 20160209 Latest Revision: 20181113
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC4620870
DOI: 10.1073/pnas.1517932112
PMID: 26438848
قاعدة البيانات: MEDLINE
الوصف
تدمد:1091-6490
DOI:10.1073/pnas.1517932112