elafin is a unique elastase inhibitor. It is differentially expressed at the transcriptional level in human normal mammary epithelial cells and carcinomas. The elafin gene is induced by PMA in 21MT2 breast tumor cells. By deletion analysis and mutagenesis, we have identified the Ap1 site in the promoter as the cis element mediating transcriptional activation of elafin in 70N normal breast cells...

The SH3 domain of the PI3 kinase (PI3-SH3 or PI3K-SH3) readily aggregates into fibrils in vitro and has served as an important model system in the investigation of the molecular properties and mechanism of formation of amyloid fibrils. We describe the molecular conformation of PI3-SH3 in amyloid fibril form as revealed by magic-angle spinning (MAS) solid-state nuclear magnetic resonance (NMR) s...

Myc synergizes with Ras and PI3-kinase in cell transformation, yet the molecular basis for this behavior is poorly understood. We now show that Myc recruits TFIIH, P-TEFb and Mediator to the cyclin D2 and other target promoters, while the PI3-kinase pathway controls formation of the pre-initiation complex and loading of RNA polymerase II. The PI3-kinase pathway involves Akt-mediated phosphoryla...

Phosphoinositide 3-kinases (PI3-kinases) are increasingly considered to have a key role in intracellular signal transduction in health and disease. Particularly the enzymes plays vital role in wide range of cancer such as breast, ovarian, myeloid leukemia, prostate, Small Cell Lung cancer (SCLC) etc., Compounds such as Wortmannin, LYS2002 are the inhibitors of PI3-kinases but these compounds sh...

While the serine/threonine protein kinase Akt has attracted attention as a mediator of survival (anti-apoptotic) signal, the regulation and function of the PI3-kinase-Akt pathway in mesangial cells is not well known. To explore the significance of the PI3-kinase-Akt pathway, this study used PI3-kinase inhibitors (Wortmannin and LY294002) and recombinant adenoviruses encoding a dominant-active m...

The phosphoinositide 3-kinase (PI3-kinase)-protein kinase B (Akt) signaling pathway is essential in the induction of physiological cardiac hypertrophy. In contrast, protein kinase C beta2 (PKCbeta2) is implicated in the development of pathological cardiac hypertrophy and heart failure. Thus far, no clear association has been demonstrated between these two pathways. In this study, we examined th...

Cells transformed by the oncogenic small GTPase, Ras, display a radioresistant phenotype in response to ionizing radiation (IR). To determine the mechanisms by which Ras mediates radioresistance in epithelial cells, we assessed the importance of three major survival pathways that can be activated by Ras [phosphatidylinositol 3-kinase (PI3-K)>Akt, nuclear factor kappaB (NF-kappaB), and Raf>mitog...

Insulin-like growth factor-I (IGF-I) plays an important role in regulating vascular smooth muscle cell (VSMC) proliferation and directed migration. The mitogenic and chemotactic actions of IGF-I are mediated through the IGF-I receptor, but how the activation of the IGF-I receptor leads to these biological responses is poorly understood. In this study, we examined the role of phosphatidylinosito...

Neurotrophins are known to regulate dendritic development, but the mechanisms that mediate neurotrophin-dependent dendrite formation are largely unknown. Here we show that brain-derived neurotrophic factor (BDNF) induces the formation of primary dendrites in cortical neurons by a protein synthesis-independent mechanism. BDNF leads to the rapid activation of PI3-kinase, MAP kinase, and PLC-gamma...