دورية أكاديمية
Identification of invariant chain CD74 as a functional receptor of tissue inhibitor of metalloproteinases-1 (TIMP-1).
| العنوان: | Identification of invariant chain CD74 as a functional receptor of tissue inhibitor of metalloproteinases-1 (TIMP-1). |
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| المؤلفون: | Schoeps B; School of Medicine, Institutes of Molecular Immunology and Experimental Oncology, Technical University of Munich, Munich, Germany., Eckfeld C; School of Medicine, Institutes of Molecular Immunology and Experimental Oncology, Technical University of Munich, Munich, Germany., Flüter L; School of Medicine, Institutes of Molecular Immunology and Experimental Oncology, Technical University of Munich, Munich, Germany., Keppler S; School of Medicine, Institute of Clinical Chemistry and Pathobiochemistry, Technical University of Munich, Munich, Germany; TranslaTUM, Center for Translational Cancer Research, Technical University Munich, Munich, Germany., Mishra R; School of Medicine, Institute of Clinical Chemistry and Pathobiochemistry, Technical University of Munich, Munich, Germany; TranslaTUM, Center for Translational Cancer Research, Technical University Munich, Munich, Germany., Knolle P; School of Medicine, Institutes of Molecular Immunology and Experimental Oncology, Technical University of Munich, Munich, Germany., Bayerl F; School of Medicine, Institutes of Molecular Immunology and Experimental Oncology, Technical University of Munich, Munich, Germany., Böttcher J; School of Medicine, Institutes of Molecular Immunology and Experimental Oncology, Technical University of Munich, Munich, Germany., Hermann CD; School of Medicine, Institutes of Molecular Immunology and Experimental Oncology, Technical University of Munich, Munich, Germany., Häußler D; School of Medicine, Institutes of Molecular Immunology and Experimental Oncology, Technical University of Munich, Munich, Germany., Krüger A; School of Medicine, Institutes of Molecular Immunology and Experimental Oncology, Technical University of Munich, Munich, Germany. Electronic address: achim.krueger@tum.de. |
| المصدر: | The Journal of biological chemistry [J Biol Chem] 2021 Sep; Vol. 297 (3), pp. 101072. Date of Electronic Publication: 2021 Aug 12. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| مواضيع طبية MeSH: | Antigens, Differentiation, B-Lymphocyte/*metabolism , Histocompatibility Antigens Class II/*metabolism , Tissue Inhibitor of Metalloproteinase-1/*metabolism, Antigens, Differentiation, B-Lymphocyte/genetics ; Antigens, Differentiation, B-Lymphocyte/ultrastructure ; Binding Sites ; Cell Line ; Histocompatibility Antigens Class II/genetics ; Histocompatibility Antigens Class II/ultrastructure ; Humans ; Intramolecular Oxidoreductases/metabolism ; Macrophage Migration-Inhibitory Factors/metabolism ; Molecular Docking Simulation ; Protein Binding ; Protein Domains ; Signal Transduction/physiology ; Tissue Inhibitor of Metalloproteinase-1/genetics ; Tissue Inhibitor of Metalloproteinase-1/ultrastructure |
| مستخلص: | Multifunctionality of tissue inhibitor of metalloproteinases-1 (TIMP-1) comprising antiproteolytic as well as cytokinic activity has been attributed to its N-terminal and C-terminal domains, respectively. The molecular basis of the emerging proinflammatory cytokinic activity of TIMP-1 is still not completely understood. The cytokine receptor invariant chain (CD74) is involved in many inflammation-associated diseases and is highly expressed by immune cells. CD74 triggers zeta chain-associated protein kinase-70 (ZAP-70) signaling-associated activation upon interaction with its only known ligand, the macrophage migration inhibitory factor. Here, we demonstrate TIMP-1-CD74 interaction by coimmunoprecipitation and confocal microscopy in cells engineered to overexpress CD74. In silico docking in HADDOCK predicted regions of the N-terminal domain of TIMP-1 (N-TIMP-1) to interact with CD74. This was experimentally confirmed by confocal microscopy demonstrating that recombinant N-TIMP-1 lacking the entire C-terminal domain was sufficient to bind CD74. Interaction of TIMP-1 with endogenously expressed CD74 was demonstrated in the Namalwa B lymphoma cell line by dot blot binding assays as well as confocal microscopy. Functionally, we demonstrated that TIMP-1-CD74 interaction triggered intracellular ZAP-70 activation. N-TIMP-1 was sufficient to induce ZAP-70 activation and interference with the cytokine-binding site of CD74 using a synthetic peptide-abrogated TIMP-1-mediated ZAP-70 activation. Altogether, we here identified CD74 as a receptor and mediator of cytokinic TIMP-1 activity and revealed TIMP-1 as moonlighting protein harboring both cytokinic and antiproteolytic activity within its N-terminal domain. Recognition of this functional TIMP-1-CD74 interaction may shed new light on clinical attempts to therapeutically target ligand-induced CD74 activity in cancer and other inflammatory diseases. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.) |
| معلومات مُعتمدة: | P41 GM103311 United States GM NIGMS NIH HHS |
| فهرسة مساهمة: | Keywords: CD74; TIMP-1; cytokine; protease inhibitor; receptor; signal transduction; signaling |
| المشرفين على المادة: | 0 (Antigens, Differentiation, B-Lymphocyte) 0 (Histocompatibility Antigens Class II) 0 (Macrophage Migration-Inhibitory Factors) 0 (TIMP1 protein, human) 0 (Tissue Inhibitor of Metalloproteinase-1) 0 (invariant chain) EC 5.3.- (Intramolecular Oxidoreductases) EC 5.3.2.1 (MIF protein, human) |
| تواريخ الأحداث: | Date Created: 20210815 Date Completed: 20211117 Latest Revision: 20211117 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC8429975 |
| DOI: | 10.1016/j.jbc.2021.101072 |
| PMID: | 34391782 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1083-351X |
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| DOI: | 10.1016/j.jbc.2021.101072 |