| http://purl.uniprot.org/citations/21875933 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21875933 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21875933 | http://www.w3.org/2000/01/rdf-schema#comment | "Macrophage-stimulating protein (MSP) is a plasminogen-related growth factor and ligand for the receptor tyrosine kinase RON. The MSP/RON system promotes wound healing and invasive tumor growth and suppresses proinflammatory immune response. MSP binding to RON requires proteolytic conversion of the inactive single-chain form (pro-MSP) into the disulfide-linked α/β heterodimer. The pro-MSP cleavage sequence (Ser-Lys-Leu-Arg(483)↓Val(484)) closely matches the substrate recognition sequences of hepsin, a type II transmembrane serine protease, that is overexpressed in several cancers. Here, we show that recombinant hepsin cleaves pro-MSP at the consensus site Arg(483)-Val(484) with superior efficiency compared with the known activators MT-SP1 and hepatocyte growth factor activator (HGFA). At least 50% of pro-MSP was processed within 1 hour at a hepsin concentration of 2.4 nmol/L and at a molar enzyme to substrate ratio of 1:500. An uncleavable single-chain variant of MSP weakly bound to a RON-Fc fusion protein, whereas hepsin-cleaved MSP bound with a K(D) of 10.3 nmol/L, suggesting that the high-affinity binding site in MSP β-chain was properly formed. LNCaP prostate cancer cells overexpressing hepsin on the cell surface efficiently activated pro-MSP, which was blocked by a specific anti-hepsin antibody. Incubation of pro-MSP with hepsin led to robust RON-mediated phosphorylation of mitogen-activated protein kinase, ribosomal S6 protein, and Akt in human A2780 ovarian carcinoma cells stably expressing RON protein. In macrophages, pro-MSP with hepsin induced chemotaxis and attenuated lipopolysaccharide-dependent production of nitric oxide. These findings suggest that the MSP/RON signaling pathway may be regulated by hepsin in tissue homeostasis and in disease pathologies, such as in cancer and immune disorders."xsd:string |
| http://purl.uniprot.org/citations/21875933 | http://purl.org/dc/terms/identifier | "doi:10.1158/1541-7786.mcr-11-0004"xsd:string |
| http://purl.uniprot.org/citations/21875933 | http://purl.org/dc/terms/identifier | "doi:10.1158/1541-7786.mcr-11-0004"xsd:string |
| http://purl.uniprot.org/citations/21875933 | http://purl.uniprot.org/core/author | "Lazarus R.A."xsd:string |
| http://purl.uniprot.org/citations/21875933 | http://purl.uniprot.org/core/author | "Lazarus R.A."xsd:string |
| http://purl.uniprot.org/citations/21875933 | http://purl.uniprot.org/core/author | "Lin S.J."xsd:string |
| http://purl.uniprot.org/citations/21875933 | http://purl.uniprot.org/core/author | "Lin S.J."xsd:string |
| http://purl.uniprot.org/citations/21875933 | http://purl.uniprot.org/core/author | "Wu T.D."xsd:string |
| http://purl.uniprot.org/citations/21875933 | http://purl.uniprot.org/core/author | "Wu T.D."xsd:string |
| http://purl.uniprot.org/citations/21875933 | http://purl.uniprot.org/core/author | "Chaudhuri A."xsd:string |
| http://purl.uniprot.org/citations/21875933 | http://purl.uniprot.org/core/author | "Chaudhuri A."xsd:string |
| http://purl.uniprot.org/citations/21875933 | http://purl.uniprot.org/core/author | "Xie M.H."xsd:string |
| http://purl.uniprot.org/citations/21875933 | http://purl.uniprot.org/core/author | "Xie M.H."xsd:string |
| http://purl.uniprot.org/citations/21875933 | http://purl.uniprot.org/core/author | "Ganesan R."xsd:string |
| http://purl.uniprot.org/citations/21875933 | http://purl.uniprot.org/core/author | "Ganesan R."xsd:string |
| http://purl.uniprot.org/citations/21875933 | http://purl.uniprot.org/core/author | "Kirchhofer D."xsd:string |
| http://purl.uniprot.org/citations/21875933 | http://purl.uniprot.org/core/author | "Kirchhofer D."xsd:string |
| http://purl.uniprot.org/citations/21875933 | http://purl.uniprot.org/core/author | "Kolumam G.A."xsd:string |
| http://purl.uniprot.org/citations/21875933 | http://purl.uniprot.org/core/author | "Kolumam G.A."xsd:string |
| http://purl.uniprot.org/citations/21875933 | http://purl.uniprot.org/core/author | "Santell L."xsd:string |
| http://purl.uniprot.org/citations/21875933 | http://purl.uniprot.org/core/author | "Santell L."xsd:string |
| http://purl.uniprot.org/citations/21875933 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21875933 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |