Dual roles of protein tyrosine phosphatase kappa in coordinating angiogenesis induced by pro-angiogenic factors

A potential role may be played by receptor-type protein tyrosine phosphatase kappa (PTPRK) in angiogenesis due to its critical function in coordinating intracellular signal transduction from various receptors reliant on tyrosine phosphorylation. In the present study, we investigated the involvement of PTPRK in the cellular functions of vascular endothelial cells (HECV) and its role in angiogenesis using in vitro assays and a PTPRK knockdown vascular endothelial cell model. PTPRK knockdown in HECV cells (HECVPTPRKkd) resulted in a decrease of cell proliferation and cell-matrix adhesion; however, increased cell spreading and motility were seen. Reduced focal adhesion kinase (FAK) and paxillin protein levels were seen in the PTPRK knockdown cells which may contribute to the inhibitory effect on adhesion. HECVPTPRKkd cells were more responsive to the treatment of fibroblast growth factor (FGF) in their migration compared with the untreated control and cells treated with VEGF. Moreover, elevated c-Src and Akt1 were seen in the PTPRK knockdown cells. The FGF-promoted cell migration was remarkably suppressed by an addition of PLCγ inhibitor compared with other small inhibitors. Knockdown of PTPRK suppressed the ability of HECV cells to form tubules and also impaired the tubule formation that was induced by FGF and conditioned medium of cancer cells. Taken together, it suggests that PTPRK plays dual roles in coordinating angiogenesis. It plays a positive role in cell proliferation, adhesion and tubule formation, but suppresses cell migration, in particular, the FGF-promoted migration. PTPRK bears potential to be targeted for the prevention of tumour associated angiogenesis

ARPES view of orbitally resolved quasiparticle lifetimes in iron pnictides

We study with ARPES the renormalization and quasiparticle lifetimes of the $d_{xy}$ and $d_{xz}$/$d_{yz}$ orbitals in two iron pnictides, LiFeAs and Ba(Fe$_{0.92}$Co$_{0.08}$)$_2$As$_2$ (Co8). We find that both quantities depend on orbital character rather than on the position on the Fermi Surface (for example hole or electron pocket). In LiFeAs, the renormalizations are larger for $d_{xy}$, while they are similar on both types of orbitals in Co8. The most salient feature, which proved robust against all the ARPES caveats we could think of, is that the lifetimes for $d_{xy}$ exhibit a markedly different behavior than those for $d_{xz}$/$d_{yz}$. They have smaller values near $E_F$ and exhibit larger $\omega$ and temperature dependences. While the behavior of $d_{xy}$ is compatible with a Fermi liquid description, it is not the case for $d_{xz}$/$d_{yz}$. This situation should have important consequences for the physics of iron pnictides, which have not been considered up to now. More generally, it raises interesting questions on how a Fermi liquid regime can be established in a multiband system with small effective bandwidths

CD73 promotes proliferation and migration of human cervical cancer cells independent of its enzyme activity

100 ΟM Adenosine treatment did not change the expression of EGFR, VEGF and Akt. (JPG 335 kb

A Morphological identification cell cytotoxicity assay using cytoplasm-localized fluorescent probe (CLFP) to distinguish living and dead cells

Cell cytotoxicity assays include cell activity assays and morphological identification assays. Currently, all frequently used cytotoxicity assays belong to cell activity assays but suffer from detection limitations. Morphological identification of cell death remains as the gold standard, although the method is difficult to scale up. At present there is no generally accepted morphological identification based cell cytotoxicity assay. In this study, we applied previous developed cell cytoplasm-localized fluorescent probe (CLFP) to display cell morphologies. Under fluorescence microscopy, the fluorescence morphology and intensity of living cells are distinct from dead cells. Based on these characters we extracted the images of living cells from series of samples via computational analysis. Thus, a novel cell morphological identification cytotoxicity assay (CLFP assay) is developed. The performance of the CLFP assay was similar to cell activity assay (MTT assay), but the accuracy of the CLFP assay was superior when measuring the cytotoxicity of active compounds.</p

DDI-CPI, a server that predicts drug–drug interactions through implementing the chemical–protein interactome

Drug–drug interactions (DDIs) may cause serious side-effects that draw great attention from both academia and industry. Since some DDIs are mediated by unexpected drug–human protein interactions, it is reasonable to analyze the chemical–protein interactome (CPI) profiles of the drugs to predict their DDIs. Here we introduce the DDI-CPI server, which can make real-time DDI predictions based only on molecular structure. When the user submits a molecule, the server will dock user's molecule across 611 human proteins, generating a CPI profile that can be used as a feature vector for the pre-constructed prediction model. It can suggest potential DDIs between the user's molecule and our library of 2515 drug molecules. In cross-validation and independent validation, the server achieved an AUC greater than 0.85. Additionally, by investigating the CPI profiles of predicted DDI, users can explore the PK/PD proteins that might be involved in a particular DDI. A 3D visualization of the drug-protein interaction will be provided as well. The DDI-CPI is freely accessible at http://cpi.bio-x.cn/ddi/