Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thrombospondin 1 is a multidomain trimeric glycoprotein from platelets and a variety of normal and transformed cells of both mesenchymal and epithelial origin, which functions in cell adhesion and cell-cell interactions. We have recently shown that human thrombospondin 1 binds and inhibits the neutrophil enzymes, neutrophil elastase [Hogg, P.J., Owensby, D.A., Mosher, D.F., Misenheimer, T.M., & Chesterman, C.N. (1993a) J. Biol. Chem. 268, 7139-7146] and cathepsin G [Hogg, P.J., Owensby, D.A., & Chesterman, C.N. (1993b) J. Biol. Chem. 268, 21811-21818]. One mole of thrombospondin 1 trimer binds 3 mol of neutrophil elastase or up to 6 mol of cathepsin G, with site-binding dissociation constants around the nanomolar range, and the enzymes have been shown to interact with thrombospondin 1 in the vicinity of the calcium-binding type 3 repeats. None of the protein modules in this region, or within the whole thrombospondin 1 molecule, have previously been implicated in the inhibition of proteinases. We noted that there are two stretches of eight amino acids each in the human thrombospondin 1 type 3 repeats, residues 735-742 and 794-801, that have striking similarity to a reactive-site consensus sequence derived from selected members of the Kazal and Streptomyces subtilisin inhibitor families. Synthetic peptides corresponding to the putative P5 through P4' residues of both proposed reactive centers interacted efficiently with the active site of cathepsin G and were competitive inhibitors of the fibronectin-degrading and platelet-activating activities of this enzyme, while only the peptide corresponding to residues 793-801 efficiently interacted with the active site of neutrophil elastase and competitively inhibited its fibronectin-degrading activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Identification of possible inhibitory reactive centers in thrombospondin 1 that may bind cathepsin G and neutrophil elastase. 820 88

The dermal papilla cells (DPCs) of hair follicles are known to secrete paracrine factors for follicular cells. Shotgun proteomic analysis was performed to compare the expression profiles of the secretomes of human DPCs and dermal fibroblasts (DFs). In this study, the proteins secreted by DPCs and matched DFs were analyzed by 1DE/LTQ FTICR MS/MS, semi-quantitatively determined using emPAI mole percent values and then characterized using protein interaction network analysis. Among the 1,271 and 1,188 proteins identified in DFs and DPCs, respectively, 1,529 were further analyzed using the Ingenuity Pathway Analysis tool. We identified 28 DPC-specific extracellular matrix proteins including transporters (ECM1, A2M), enzymes (LOX, PON2), and peptidases (C3, C1R). The biochemically- validated DPC-specific proteins included thrombospondin 1 (THBS1), an insulin-like growth factor binding protein3 (IGFBP3), and, of particular interest, an integrin beta1 subunit (ITGB1) as a key network core protein. Using the shotgun proteomic technique and network analysis, we selected ITGB1, IGFBP3, and THBS1 as being possible hair-growth modulating protein biomarkers.
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PMID:Comparative secretome analysis of human follicular dermal papilla cells and fibroblasts using shotgun proteomics. 2253 Nov 37