HER2 stabilizes survivin while concomitantly down-regulating survivin gene transcription by suppressing Notch cleavage
In breast cancer, the HER2 receptor tyrosine kinase is associated with extremely poor prognosis and survival. Notch signaling has a key role in cell-fate decision especially in cancer-initiating cells. The Notch intracellular domain produced by Notch cleavage is translocated to the nucleus where it activates transcription of target genes. To determine the combinatory effect of HER2 and Notch signaling in breast cancer, we investigated the effect of HER2 on Notch-induced cellular phenomena. We found the down-regulation of Notch-dependent transcriptional activity by HER2 overexpression. Also, the HER2/ERK signal pathway down...
Source: BJ Cell - January 17, 2013 Category: Biochemistry Authors: J Ju, W Yang, S Oh, K Nam, K Lee, D Noh, I Shin Tags: BJ Signal Source Type: research
Saltatory formation, sliding and dissolution of ER-PM junctions in migrating cancer cells
We demonstrated three novel forms of dynamic behaviour of junctions between the endoplasmic reticulum (ER) and the plasma membrane (PM) in migrating cancer cells: saltatory formation, long distance sliding and dissolution. The individual ER-PM junctions formed near the leading edge of migrating cells (usually within 0.5µm of polymerised actin and close to focal adhesions) and appeared suddenly without sliding from the interior of the cell. The long distance sliding and dissolution of ER-PM junctions accompanied the tail withdrawal. (Source: BJ Cell)
Source: BJ Cell - January 16, 2013 Category: Biochemistry Authors: H Dingsdale, E Okeke, M Awais, L P Haynes, D N Criddle, R Sutton, A V Tepikin Tags: BJ Cell Source Type: research
Hepatocyte growth factor activator inhibitor type 2 (HAI-2) modulates hepcidin expression by inhibiting cell surface protease matriptase-2
Matriptase-2, a recently identified cell surface protease is the key enzyme of iron homeostasis modulating the expression of the liver peptide hormone hepcidin. Hepatocyte growth factor activator inhibitors type 1 and 2 (HAI-1 and HAI-2) have been shown to inhibit the close homologue, i.e. matriptase. By co-expressing matriptase-2 and the inhibitor HAI-2 we have identified HAI-2 displaying high inhibitory potential against matriptase-2 at the cell surface as well as in conditioned media. Accordingly, complex formation between matriptase-2 and HAI-2 was demonstrated by isolation of the complex via immobilizing either HAI-2 ...
Source: BJ Cell - January 8, 2013 Category: Biochemistry Authors: E Maurer, M Gütschow, M Stirnberg Tags: BJ Cell Source Type: research
Extracellular Calcium influx activates Adenylate Cyclase 1 and potentiates Insulin secretion in MIN6 cells
In this study, we investigated the interplay between intracellular cAMP and Ca2+ concentrations ([cAMP]i and [Ca2+]i, respectively) in the pancreatic β cell line MIN6 cells using total internal reflection fluorescence microscopy. For measuring [cAMP]i, we developed a genetically encoded yellow fluorescent biosensor for cAMP (fluorescent cAMP indicator; Flamindo), which changes fluorescence intensity with cAMP binding. Application of high-KCl or glucose to MIN6 cells induced the elevation of [cAMP]i and exocytosis. Furthermore, application of an L-type Ca2+ channel agonist or ionomycin to induce ...
Source: BJ Cell - January 3, 2013 Category: Biochemistry Authors: T Kitaguchi, M Oya, Y Wada, T Tsuboi, A Miyawaki Tags: BJ Cell Source Type: research
Time-resolved metabolomics analysis of {Sharp S}-cells implicates the pentose phosphate pathway in the control of insulin release
Insulin secretion is coupled to changes in ß-cell metabolism. To define this process, 195 putative metabolites, mitochondrial respiration, NADP+, NADPH, and insulin secretion were measured within 15 minutes after stimulation of clonal INS-1 832/13 ß-cells with glucose. Rapid responses in the major metabolic pathways of glucose occurred, involving several previously suggested metabolic coupling factors. The complexity of metabolite changes observed disagreed with the concept of one single metabolite controlling insulin secretion. The complex alterations in metabolite levels suggest that a coupling signa...
Source: BJ Cell - January 2, 2013 Category: Biochemistry Authors: P Spégel, V V. Sharoyko, I Göhring, A P.H. Danielsson, S Malmgren, C L.F. Nagorny, L E Andersson, T Koeck, G W.G. Sharp, S G Straub, C B Wollheim, H Mulder Tags: BJ Metabolism Source Type: research
