Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mast cells (MC) can be stimulated to secrete by cross-linking immunoglobulin E bound to specific surface receptors, as well as in response to polycationic molecules such as substance P and compound 48/80. The antiallergic drug disodium cromoglycate (cromolyn) inhibited MC secretion and rapidly incorporated phosphate into a 78 kDa protein, speculated to be its mode of action. This protein was purified by single and two-dimensional gel electrophoresis, and was shown to be phosphorylated primarily on serine residues by protein kinase C. Partial amino acid sequencing of two generated fragments was identical to that of portions of mouse moesin, a member of the band 4.1 superfamily of proteins, with no definitive function known to date. Polyclonal antibodies raised against the rat basophil leukemia cell moesin cDNA expressed in Escherichia coli immunoprecipitated the 78 kDa phosphoprotein quantitatively, and immunocytochemistry localized it to the plasma membrane. Reversible phosphorylation of this 78 kDa phosphoprotein could affect its possible cytoskeletal binding through which it may regulate stimulus-secretion coupling in MC.
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PMID:Characterization of the 78 kDa mast cell protein phosphorylated by the antiallergic drug cromolyn and homology to moesin. 868 95

Neutral endopeptidase 24.11 (NEP) is a 90-110 kDa cell surface cell surface peptidase that is normally expressed by numerous tissues, including prostate, kidney, intestine, endometrium, adrenal glands and lung. This enzyme cleaves peptide bonds on the amino side of hydrophobic amino acids and inactivates a variety of physiologically active peptides, including atrial natriuretic factor, substance P, bradykinin, oxytocin, Leu- and Met-enkephalins, neurotensin, bombesin, endothelin-1, and bombesin-like peptides. NEP reduces the local concentration of peptide available for receptor binding and signal transduction. Loss or decreases in NEP expression have been reported in a variety of malignancies. Reduced NEP may promote peptide-mediated proliferation by allowing accumulation of higher peptide concentrations at the cell surface, and facilitate the development or progression of neoplasia. We have used prostate cancer as model in which to study the involvement of NEP in malignancy. Using a variety of experimental approaches, including recombinant NEP, cell lines expressing wild-type and mutant NEP protein, and cell lines expressing NEP protein with a mutated cytoplasmic domain, we have examined the effects of NEP on cell migration and cell survival. We have shown that the effects of NEP are mediated by its ability to catalytically inactivate substrates such as bombesin and endothelin-1, but also through direct protein-protein interaction with other protein such as Lyn kinase [which associates with the p85 subunit of phosphatidylinositol 3-kinase (PI3-K) resulting in NEP-Lyn-PI3-K protein complex], ezrin/radixin/moesin (ERM) proteins, and the PTEN tumor suppressor protein. We review the mechanisms of NEP's tumor suppressive action and how NEP loss contributes to tumor progression.
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PMID:Involvement of neutral endopeptidase in neoplastic progression. 1605 17

Peptidases are emerging as promising drug targets in tumour suppression. Neprilysin, also known as neutral endopeptidase, is a cell surface peptidase that degrades various peptides such as angiotensin II, endothelin I, Substance P, etc., and reduces their local concentration. Neprilysin is expressed in various tissues such as kidney, prostate, lung, breast, brain, intestine, adrenal gland, etc. The tumour-suppressor mechanisms of neprilysin include its peptidase activity that degrades mitogenic growth factors such as fibroblast growth factor-2 and insulin-like growth factors, and the protein-protein interaction of neprilysin with phosphatase and tensin homolog, focal adhesion kinase, ezrin/radixin/moesin, and phosphoinositide 3-kinase. Studies have shown that the levels of neprilysin play an important role in malignancies. NEP is downregulated in prostate, renal, lung, breast, urothelial, cervical, hepatic cancers, etc. Histone deacetylation and hypermethylation of the neprilysin promoter region are the common mechanisms involved in the downregulation of neprilysin. Downregulation of the peptidase promotes angiogenesis, cell survival and cell migration. This review presents an overview of the role of neprilysin in malignancy, the tumour suppression mechanisms of neprilysin, the epigenetic mechanisms responsible for downregulation of neprilysin, and the potential pharmacological approaches to upregulate neprilysin levels and its activity.
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PMID:Tumour suppression through modulation of neprilysin signaling: A comprehensive review. 3316 Sep 35