ArticleiScience2018
Extracellular Phosphorylation of TIMP-2 by Secreted c-Src Tyrosine Kinase Controls MMP-2 Activity.
Article in iScience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- Neonatal hyperoxia promotes macrophage senescence and lung injury via a p38MAPK-dependent secretome.American journal of respiratory cell and molecular biology · 2026Article
- Hsp90: Bringing it all together.Cell stress & chaperones · 2025Review
- Chemoproteomics reveals immunogenic and tumor-associated cell surface substrates of ectokinase CK2α.Cell chemical biology · 2024Article
- Chemoproteomics reveals immunogenic and tumor-associated cell surface substrates of ectokinase CK2α.bioRxiv : the preprint server for biology · 2024Article
- The TIMP protein family: diverse roles in pathophysiology.American journal of physiology. Cell physiology · 2024Review
- Second international symposium on the chaperone code, 2023.Cell stress & chaperones · 2024Article
- Extracellular Proximity Labeling Reveals an Expanded Interactome for the Matrisome Protein TIMP2.Research square · 2024Article
- Mutations F352A and Y528A in human HSP90α reduce fibronectin association and fibrillogenesis in cell-derived matrices.Cell stress & chaperones · 2023Article
- Tissue inhibitors of metalloproteinases are proteolytic targets of matrix metalloproteinase 9.Matrix biology : journal of the International Society for Matrix Biology · 2023Article
- The Continuing Saga of Tissue Inhibitor of Metalloproteinase 2: Emerging Roles in Tissue Homeostasis and Cancer Progression.The American journal of pathology · 2023Review
- PhosY-secretome profiling combined with kinase-substrate interaction screening defines active c-Src-driven extracellular signaling.Cell reports · 2023Article
- Tenth International Symposium on the Hsp90 chaperone machine : Switzerland, October 19-23, 2022.Cell stress & chaperones · 2023Review
- Methods to Assess the Impact of Hsp90 Chaperone Function on Extracellular Client MMP2 Activity.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Impact of Co-chaperones and Posttranslational Modifications Toward Hsp90 Drug Sensitivity.Sub-cellular biochemistry · 2023Article
- Knock down of TIMP-2 by siRNA and CRISPR/Cas9 mediates diverse cellular reprogramming of metastasis and chemosensitivity in ovarian cancer.Cancer cell international · 2022Article
- Unravelling the distinct biological functions and potential therapeutic applications of TIMP2 in cancer.Carcinogenesis · 2022Review
- The Biology and Function of Tissue Inhibitor of Metalloproteinase 2 in the Lungs.Pulmonary medicine · 2022Review
- Targeting extracellular Hsp90: A unique frontier against cancer.Frontiers in molecular biosciences · 2022Review
- Src family kinases, adaptor proteins and the actin cytoskeleton in epithelial-to-mesenchymal transition.Cell communication and signaling : CCS · 2021Review
- MMPs, tyrosine kinase signaling and extracellular matrix proteolysis in kidney cancer.Urologic oncology · 2021Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The tissue inhibitor of metalloproteinases 2 (TIMP-2) is a specific endogenous inhibitor of matrix metalloproteinase 2 (MMP-2), which is a key enzyme that degrades the extracellular matrix and promotes tumor cell invasion. Although the TIMP-2:MMP-2 complex controls proteolysis, the signaling mechanism by which the two proteins associate in the extracellular space remains unidentified. Here we report that TIMP-2 is phosphorylated outside the cell by secreted c-Src tyrosine kinase. As a consequence, phosphorylation at Y90 significantly enhances TIMP-2 potency as an MMP-2 inhibitor and weakens the catalytic action of the active enzyme. TIMP-2 phosphorylation also appears to be essential for its interaction with the latent enzyme proMMP-2 in vivo. Absence of the kinase or non-phosphorylatable Y90 abolishes TIMP-2 binding to the latent enzyme, ultimately hampering proMMP-2 activation. Together, TIMP-2 phosphorylation by secreted c-Src represents a critical extracellular regulatory mechanism that controls the proteolytic function of MMP-2.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.