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Growth factors can promote cell survival by activating the phosphatidylinositide-3'-OH kinase and its downstream target, the serine-threonine kinase Akt. However, the mechanism by which Akt functions to promote survival is not understood. We show that growth factor activation of the PI3'K/Akt signaling pathway culminates in the phosphorylation of the BCL-2(More)
The 14-3-3 proteins are a family of conserved regulatory molecules expressed in all eukaryotic cells. A striking feature of the 14-3-3 proteins is their ability to bind a multitude of functionally diverse signaling proteins, including kinases, phosphatases, and transmembrane receptors. This plethora of interacting proteins allows 14-3-3 to play important(More)
The 14-3-3 proteins are a family of highly conserved eukaryotic regulatory molecules that play important roles in many biological processes including cell cycle control and regulation of cell death. They are able to carry out these effects through binding and modulating the activity of a host of signaling proteins. The ability of 14-3-3 to inhibit Bad and(More)
Polycystic ovaries (PCO) are detected using ultrasonography in a proportion of women who do not have clinical symptoms of the polycystic ovary syndrome (PCOS). The aim of this study was to compare the metabolic and endocrine differences between women with such ultrasound-detected PCO and women with PCOS, and to relate these changes to clinical presentation(More)
14-3-3 proteins bind a variety of molecules involved in signal transduction, cell cycle regulation and apoptosis. 14-3-3 binds ligands such as Raf-1 kinase and Bad by recognizing the phosphorylated consensus motif, RSXpSXP, but must bind unphosphorylated ligands, such as glycoprotein Ib and Pseudomonas aeruginosa exoenzyme S, via a different motif. Here we(More)
The 14-3-3 proteins are a family of conserved, dimeric proteins that interact with a diverse set of ligands, including molecules involved in cell cycle regulation and apoptosis. It is well-established that 14-3-3 binds to many ligands through phosphoserine motifs. Here we characterize the interaction of 14-3-3 with a nonphosphorylated protein ligand, the(More)
OBJECTIVE To examine different patterns of glucose and insulin secretion in women (of both Indian and white ethnic backgrounds) with polycystic ovary syndrome (PCOS). DESIGN A 75-g oral glucose tolerance test was performed in 11 subjects from each group. SETTING Reproductive Medicine and Gynecological Clinics from The Queen Elizabeth Hospital,(More)
Through interaction with a multitude of target proteins, 14-3-3 proteins participate in the regulation of diverse cellular processes including apoptosis. These 14-3-3-interacting proteins include a proapoptotic Bcl-2 homolog, Bad (Bcl-2/Bcl-XL-associated death promoter). To understand how 14-3-3 interacts with Bad and modulates its function, we have(More)
OBJECTIVES To examine the relationship between various hormonal and metabolic variables in a large group of women with unequivocal evidence of polycystic ovarian syndrome (PCOS) to dissect out the metabolic heterogeneity of this condition. DESIGN Cross-sectional observational study of PCOS (n = 122) and non-PCOS (n = 26) subjects. SETTING Reproductive(More)
BAD is a proapoptotic member of the BCL-2 family of proteins, which play a major role in regulating apoptosis in cytokine-dependent hematopoietic cells. The function of BAD is regulated by reversible phosphorylation. Deprivation of survival factors induces BAD dephosphorylation, resulting in apoptosis. Serine-threonine phosphatase activity dephosphorylated(More)