Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myelodysplastic syndromes are characterized by a high risk of evolution into acute myeloid leukaemia which can involve activation of signalling pathways. As the chaperone heat shock protein 90 (HSP90) has a key role in signal transduction, we investigated its role in the pathogenesis and evolution of myelodysplastic syndromes. Expressions of HSP90 and signalling proteins clients (phosphorylated-AKT (pAKT), Focal Adhesion Kinase (FAK) and phosphorylated-FAK (pFAK)), were assessed in bone marrow mononuclear and CD34-positive (CD34+) cells from 177 patients with myelodysplasia. Effects of HSP90 inhibition were also evaluated in 39 samples. The levels of all proteins studied were significantly higher in patients with high grade disease, than those with low grade myelodysplastic syndrome or chronic myelomonocytic leukaemia. High levels of HSP90, FAK, pFAK and pAKT were associated with shorter survival and increased risk of progression into acute leukaemia. A down regulation of pFAK and pAKT and increased apoptosis was observed in mononuclear and CD34+ cells after 12 hours of incubation with 17-AAG. In conclusion, our data suggest the implication of HSP90 and FAK and AKT activation in the pathogenesis of myelodysplastic syndromes with excess of blasts and evolution to leukaemia. Moreover this signalling network could be a therapeutic target through HSP90 inhibition.
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PMID:Heat Shock Protein 90 is overexpressed in high-risk myelodysplastic syndromes and associated with higher expression and activation of Focal Adhesion Kinase. 2304 54

Adhesion of calcium oxalate monohydrate (COM) crystals on renal tubular epithelial cells is a crucial step in kidney stone formation. Finding potential crystal receptors on the apical membrane of the cells may lead to a novel approach to prevent kidney stone disease. Our previous study identified a large number of crystal-binding proteins on the apical membrane of MDCK cells. However, their functional role as potential crystal receptors had not been validated. The present study aimed to address the potential role of heat shock protein 90 (HSP90) as a COM crystal receptor. The apical membrane was isolated from polarized MDCK cells by the peeling method and recovered proteins were incubated with COM crystals. Western blot analysis confirmed the presence of HSP90 in the apical membrane and the crystal-bound fraction. Immunofluorescence staining without permeabilization and laser-scanning confocal microscopy confirmed the surface HSP90 expression on the apical membrane of the intact cells. Crystal adhesion assay showed that blocking surface HSP90 by specific anti-HSP90 antibody and knockdown of HSP90 by small interfering RNA (siRNA) dramatically reduced crystal binding on the apical surface of MDCK cells (by approximately 1/2 and 2/3, respectively). Additionally, crystal internalization assay revealed the presence of HSP90 on the membrane of endocytic vesicle containing the internalized COM crystal. Moreover, pretreatment of MDCK cells with anti-HSP90 antibody significantly reduced crystal internalization (by approximately 1/3). Taken together, our data indicate that HSP90 serves as a potential receptor for COM crystals on the apical membrane of renal tubular epithelial cells and is involved in endocytosis/internalization of the crystals into the cells.
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PMID:Surface heat shock protein 90 serves as a potential receptor for calcium oxalate crystal on apical membrane of renal tubular epithelial cells. 2711 9