ArticleProceedings of the National Academy of Sciences of the United States of America2007
Coordinate expression and functional profiling identify an extracellular proteolytic signaling pathway.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 99 citations in OpenAlex.
- MSP-RON signaling in liver pathobiology and as an emerging therapeutic target: a review of the current evidence.Cell communication and signaling : CCS · 2025Review
- Matriptase-dependent epidermal pre-neoplasm in zebrafish embryos caused by a combination of hypotonic stress and epithelial polarity defects.PLoS genetics · 2023Article
- The serine protease matriptase inhibits migration and proliferation in multiple myeloma cells.Oncotarget · 2022Article
- Opportunities and challenges of targeting c-Met in the treatment of digestive tumors.Frontiers in oncology · 2022Review
- The Emerging Role of c-Met in Carcinogenesis and Clinical Implications as a Possible Therapeutic Target.Journal of oncology · 2022Review
- Aberrant regulation favours matriptase proteolysis in neoplastic B-cells that co-express HAI-2.Journal of enzyme inhibition and medicinal chemistry · 2019Article
- Ectopic expression of human airway trypsin-like protease 4 in acute myeloid leukemia promotes cancer cell invasion and tumor growth.Cancer medicine · 2019Article
- MSP-RON Signaling Is Activated in the Transition From Pancreatic Intraepithelial Neoplasia (PanIN) to Pancreatic Ductal Adenocarcinoma (PDAC).Frontiers in physiology · 2019Article
- RON kinase inhibition reduces renal endothelial injury in sickle cell disease mice.Haematologica · 2018Article
- Engineering a potent inhibitor of matriptase from the natural hepatocyte growth factor activator inhibitor type-1 (HAI-1) protein.The Journal of biological chemistry · 2018Article
- Development of a Protease Biosensor Based on a Dimerization-Dependent Red Fluorescent Protein.ACS chemical biology · 2018Article
- Hypoxia-inducible factor 1α is Essential for Macrophage-mediated Erythroblast Proliferation in Acute Friend Retrovirus Infection.Scientific reports · 2017Article
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- The role of type II transmembrane serine protease-mediated signaling in cancer.The FEBS journal · 2017Review
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- Qingchang Wenzhong Decoction Attenuates DSS-Induced Colitis in Rats by Reducing Inflammation and Improving Intestinal Barrier Function via Upregulating the MSP/RON Signalling Pathway.Evidence-based complementary and alternative medicine : eCAM · 2017Article
- Selective Inhibition of Prostasin in Human Enterocytes by the Integral Membrane Kunitz-Type Serine Protease Inhibitor HAI-2.PloS one · 2017Article
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- Matriptase promotes inflammatory cell accumulation and progression of established epidermal tumors.Oncogene · 2015Article
- Matriptase and MET are prominently expressed at the site of bone metastasis in renal cell carcinoma: immunohistochemical analysis.Human cell · 2015Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A multidisciplinary method combining transcriptional data, specificity profiling, and biological characterization of an enzyme may be used to predict novel substrates. By integrating protease substrate profiling with microarray gene coexpression data from nearly 2,000 human normal and cancerous tissue samples, three fundamental components of a protease-activated signaling pathway were identified. We find that MT-SP1 mediates extracellular signaling by regulating the local activation of the prometastatic growth factor MSP-1. We demonstrate MT-SP1 expression in peritoneal macrophages, and biochemical methods confirm the ability of MT-SP1 to cleave and activate pro-MSP-1 in vitro and in a cellular context. MT-SP1 induced the ability of MSP-1 to inhibit nitric oxide production in bone marrow macrophages. Addition of HAI-1 or an MT-SP1-specific antibody inhibitor blocked the proteolytic activation of MSP-1 at the cell surface of peritoneal macrophages. Taken together, our work indicates that MT-SP1 is sufficient for MSP-1 activation and that MT-SP1, MSP-1, and the previously shown MSP-1 tyrosine kinase receptor RON are required for peritoneal macrophage activation. This work shows that this triad of growth factor, growth factor activator protease, and growth factor receptor is a protease-activated signaling pathway. Individually, MT-SP1 and RON overexpression have been implicated in cancer progression and metastasis. Transcriptional coexpression of these genes suggests that this signaling pathway may be involved in several human cancers.
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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.