Prostatic branching morphogenesis is an intricate event requiring precise temporal and spatial integration of numerous hormonal and growth factor-regulated inputs, yet relatively little is known about the downstream signaling pathways that orchestrate this process. In this study, we use a novel mesenchyme-free embryonic prostate culture system, newly available mTOR inhibitors and a conditional ...

Rho-mediated inhibition of myosin light chain (MLC) phosphatase (MLCP), together with Ca(2+)-dependent MLC kinase activation, constitutes the major signaling mechanisms for vascular smooth muscle contraction. We recently unveiled the involvement of Ca(2+)-induced, phosphoinositide 3-kinase (PI3K) class IIα isoform (PI3K-C2α)-dependent Rho activation and resultant Rho kinase-dependent MLCP suppr...

Ligand activation of the metabotropic glutamate receptor (mGluR) activates the lipid kinase PI3K in both the mammalian central nervous system and Drosophila motor nerve terminal. In several subregions of the mammalian brain, mGluR-mediated PI3K activation is essential for a form of synaptic plasticity termed long-term depression (LTD), which is implicated in neurological diseases such as fragil...

Growth factors and other stimuli increase the activity of phosphatidylinositol-3 kinase (PI3K), an SH2 domain-containing lipid kinase. In the murine kidney inner medullary mIMCD3 cell line, urea (200 mM) increased PI3K activity in a time-dependent fashion as measured by immune complex kinase assay. The PI3K effector, Akt, was also activated by urea as measured by anti-phospho-Akt immunoblotting...

In peripheral tissues, insulin signaling involves activation of the insulin receptor substrate (IRS)-phosphatidylinositol 3-kinase (PI3K) enzyme system. In the hypothalamus, insulin functions with leptin as an afferent adiposity signal important for the regulation of body fat stores and hepatic glucose metabolism. To test the hypothesis that hypothalamic insulin action involves intracellular PI...

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 ...