The PI3K pathway is genetically altered in excess of 70% of breast cancers, largely through PIK3CA mutation and HER2 amplification. Preclinical studies have suggested that these subsets of breast cancers are particularly sensitive to PI3K inhibitors; however, the reasons for this heightened sensitivity are mainly unknown. We investigated the signaling effects of PI3K inhibition in PIK3CA mutant...

The aim of this study was to investigate the correlation between Girdin and PI3K in breast cancer stem cells and the clinical implications of the co-expression of these two proteins in breast cancer patients. CD44+/CD24- tumor cells from the MD-231 cell line were sorted by flow cytometry. The expression status of Girdin and PI3K proteins was detected using western blotting and immunohistochemic...

Phosphatidylinositol 3-kinase (PI3K) has numerous cellular functions, including cell survival and proliferation. In this study, we demonstrated that the expression of the active form of PI3K induced dorsal differentiation and axis duplication and strongly induced the expression of neural markers. In contrast, the inhibition of PI3K activity by its dominant negative mutant induced the phenotype ...

The PI3K (phosphoinositide 3-kinase) signalling pathway promotes proliferation and transformation in many cell types. This is particularly well illustrated by studies of primary lymphocytes and their leukaemic counterparts. PI3K activation is required for proliferation of T cells and B cells, and certain oncogenes cause leukaemia in part by promoting PI3K signalling. Genetic manipulation of thi...

PI3K (phosphoinositide 3-kinase) is a key regulator of cell growth, metabolism and survival. The frequent activation of the PI3K pathway in cancer has stimulated widespread interest in identifying potent and selective inhibitors of PI3K isoforms. The present paper highlights recent progress in identifying such molecules and the challenges that remain for efforts to pharmacologically target the ...

In this study, we present findings that suggest that PI3K-C2α, a member of the class II phosphoinositide 3-kinase (PI3K) subfamily, regulates the process of FcεRI-triggered degranulation. RBL-2H3 cells were transfected with shRNA targeting PI3K-C2α. The knockdown impaired the FcεRI-induced release of a lysosome enzyme, β-hexosaminidase, without affecting the intracellular Ca2+ mobilization. The...

Recent studies demonstrated a role for hypothalamic insulin and leptin action in the regulation of glucose homeostasis. This regulation involves proopiomelanocortin (POMC) neurons because suppression of phosphatidyl inositol 3-kinase (PI3K) signaling in these neurons blunts the acute effects of insulin and leptin on POMC neuronal activity. In the current study, we investigated whether disruptio...

Phosphoinositide 3-Kinase (PI3K) is a central enzyme in a signaling pathway that mediates cellular responses to insulin and other growth factors. This enzyme phosphorylates the 3 position of phosphatidylinositol-4,5-bisphosphate to produce phosphatidyl-inositol-3,4,5-trisphosphate (PIP3) at the plasma membrane. A number of signaling proteins, including the Ser/Thr protein kinases, AKT and PDK1,...

Romidepsin (FK228, depsipeptide) is a potent histone deacetylase (HDAC) inhibitor that has FDA approval for the treatment of cutaneous and peripheral T-cell lymphomas. We have previously reported that FK228 and its analogs have an additional activity as phosphatidylinositol 3-kinase (PI3K) inhibitors, and are defined as HDAC/PI3K dual inhibitors. Because a combination of an HDAC inhibitor and a...

Rho-mediated inhibition of myosin light chain (MLC) phosphatase (MLCP), together with Ca -dependent MLC kinase activation, constitutes the major signaling mechanisms for vascular smooth muscle contraction. We recently unveiled the involvement of Ca -induced, phosphoinositide 3-kinase (PI3K) class II isoform (PI3K-C2 )– dependent Rho activation and resultant Rho kinase-dependent MLCP suppression...