Disease relevance of MST1

• In this report, we used an antibody phage display library to generate IMC-41A10, a human immunoglobulin G1 (IgG1) antibody that binds with high affinity (ED(50) = 0.15 nmol/L) to RON and effectively blocks interaction with its ligand, macrophage-stimulating protein (MSP; IC(50) = 2 nmol/L) [1].
• A human hepatoma (HepG2) cell line library was screened with an oligonucleotide probe for macrophage stimulating protein (MSP) to clone an MSP cDNA [2].
• The DNF15S2 locus has been proposed to code for one or more tumor suppressor genes since this locus is deleted in DNA from small cell lung carcinoma, other lung cancers, renal cell carcinoma, and von Hippel-Lindau syndrome [3].
• MSP mRNA expression in endometrial epithelial cells was significantly up-regulated in endometriosis patients during the late secretory phase compared with expression in controls [4].
• Nitrosamine-treated hamsters also demonstrate pulmonary neuroendocrine cell apoptosis in situ during the same time period as expression of the endogenous HGFL/ MSP gene, immediately preceding the spontaneous regression of neuroendocrine cell hyperplasia [5].

Psychiatry related information on MST1

• A comparison of speech perception of cochlear implantees using the Spectral Maxima Sound Processor (SMSP) and the MSP (MULTIPEAK) processor [6].
• The unidimensionality and cumulativeness of the subscales Health Perceptions, Mental Health, Physical Pain, and Social Functioning of the MOS Short-form General Health Survey were investigated using the Mokken Scale Analysis for Polychotomous Items (MSP) [7].

High impact information on MST1

• MSP caused phosphorylation of the beta chain of Ron and induced migration of MDCK-RE7 cells [8].
• Labeled MSP bound to Madin-Darby canine kidney (MDCK) cells transfected with complementary DNA encoding Ron, a cell membrane protein tyrosine kinase [8].
• Ron, the tyrosine kinase receptor for the Macrophage-stimulating protein, is involved in cell dissociation, motility, and matrix invasion [9].
• In addition to making mouse resident peritoneal macrophages responses to chemoattractants, MSP caused the appearance of long cytoplasmic processes and pinocytic vesicles in freshly plated macrophages [10].
• Whereas resident peritoneal macrophages bind but do not ingest sheep erythrocytes opsonized with IgM anti-Forssman antibody and mouse C3b, addition of MSP caused ingestion [10].

Chemical compound and disease context of MST1

• We wished to test the hypothesis that MSP and its tyrosine kinase receptor, RON, might represent an autocrine/paracrine system involved in the pathogenesis of human nonneuroendocrine lung tumors, the non-small-cell carcinomas (NSCLCs) [11].
• Mefloquine is the treatment of choice for uncomplicated multiresistant falciparum malaria, and in combination with sulphadoxine and pyrimethamine (MSP) at a single dose of 15/30/1.5 mg/kg, respectively, has been used in Thailand for the past 6 years [12].
• Bisulfite-modified DNA sequencing and MSP assay showed aberrant methylation of TIMP-2 5'-CpG island in 17 of 36 (47%) invasive cervical carcinomas and in 2 of 3 cervical cancer cell lines [13].
• Previous experiments have shown that a Synechocystis sp. PCC 6803 mutant (delta psbO) lacking the extrinsic manganese-stabilizing protein (MSP) exhibits impaired, but significant levels of H2O-splitting activity [Burnap, R., & Sherman, L.A. (1991) Biochemistry 30, 440-446] [14].
• To this end, we undertook a comparative controlled trial of the new triple combination, mefloquine-sulphadoxine-pyrimethamine (MSP, Fansimef) with chloroquine in a group of Nigerian children with symptomatic falciparum malaria [15].

Biological context of MST1

• MST1-induced apoptosis is suppressed by a dominant interfering mutant of p53 [16].
• These findings indicate that the ciliated epithelium of the mucociliary transport apparatus is a novel target of MSP [17].
• Forced downregulation of MSP expression in H1299 cells, derived from a large-cell lung carcinoma, confers increased resistance against etoposide-induced cell death [18].
• Thus, repression of MSP gene expression by mutant p53 may contribute to oncogenesis in a cell type-specific manner [18].
• Macrophage stimulating protein (MSP) belongs to the plasminogen-related kringle domain family [19].

Anatomical context of MST1

• An overexpressed inactive MST1 mutant associates in COS-7 cells with an endogenous 761-amino acid polypeptide known as "death-associated protein 4" (DAP4) [16].
• MSP bound to RON on normal human bronchial epithelial cells with a high affinity (Kd = 0.5 nM) and induced autophosphorylation of RON [17].
• Macrophage-stimulating protein (MSP) is an 80-kD serum protein with homology to hepatocyte growth factor (HGF) [17].
• The MSP-RON signaling pathway has been implicated in the functional regulation of mononuclear phagocytes [17].
• Murine resident peritoneal macrophages have two cell surface proteolytic activities that cleave pro-MSP [20].

Associations of MST1 with chemical compounds

• MST1 is predominantly cytoplasmic, but cycles continuously through the nucleus, as evidenced by its rapid accumulation in the nucleus after addition of the Crm1 inhibitor, leptomycin B [16].
• Therapeutic Implications of a Human Neutralizing Antibody to the Macrophage-Stimulating Protein Receptor Tyrosine Kinase (RON), a c-MET Family Member [1].
• We show that growth factor macrophage stimulating protein (MSP)- and its receptor Ron-mediated PI3K activation in keratinocytes induces phosphorylation of both Ron and alpha6beta4 integrin at specific 14-3-3 binding sites [21].
• Chondroitinase AC-treated proteoglycans react with MST1, indicating that the antibody does not recognize chondroitin sulfate [22].
• 3. Using MST1 we were able to demonstrate that both PG1 and PG2 aggregate with hyaluronic acid [22].

Regulatory relationships of MST1

• HK2 produced MSP and expressed RON in a form that was phosphorylated by rMSP [23].
• On the contrary, MSP-induced IL-10 release is higher in AM from healthy non-smokers [24].
• This caspase activation and apoptotic changes occur through JNK, since the co-expression of a dominant-negative mutant of JNK inhibited MST1-induced morphological changes as well as caspase activation [25].
• In this study, we evaluated whether IL-15 regulates the macrophage stimulatory pathways governing inflammatory events that take place in the lung of patients with HIV infection [26].

Other interactions of MST1

• Our findings suggest that the MSP-RON signaling pathway is a novel regulatory system of mucociliary function and might be involved in the host defense and fertilization [17].
• The beta-chain of MSP has three extra cysteines, Cys527, Cys562, and Cys672, which are not found in the plasminogen beta-chain [27].
• Further, MSP-dependent beta4 tyrosine phosphorylation evokes p38 and NF-kappaB signaling required for keratinocyte wound closure [21].
• Besides inducing interleukin-1 beta (IL-1beta) and interleukin-10 (IL-10) production, MSP triggers an enhanced tumor necrosis factor-alpha release, especially in healthy and pulmonary fibrosis smokers [24].
• MSP activates the transcription factor NF-kappaB; this effect is more potent in healthy and fibrosis smokers (2.5-fold increase in p50 subunit translocation) [24].
• Accordingly, MST1 mediates the nuclear translocation of FOXO1 in primary rat cerebellar granule neurons that are deprived of neuronal activity [28].

Analytical, diagnostic and therapeutic context of MST1

• The ability of ron-sema to suppress growth of MSP-responsive cells in culture, including cancer cells, points to a potential therapeutic use of this molecule, and forced expression of it could potentially be used as a gene therapy tool for treating MSP-dependent types of cancer [29].
• MSP protein was evaluated by Western blot in supernatant of cultured human tubular cells (HK2) and human mesangial cells (HMC) [23].
• MSP mRNA was investigated in HK2 by reverse transcription-polymerase chain reaction (RT-PCR) [23].
• The expression of MSP and RON in normal human renal tissue was studied by immunohistochemistry [23].
• This was reflected in Northern blots probed with an MSP cDNA, which showed more than one mRNA species [2].

References