The purpose of this study was to determine if PKB signaling is decreased and contractile protein degradation is increased in extensor digitorum longus (EDL) and soleus (SOL) muscles from middle-aged (MA) and aged (AG) mice. We also examined the effect of age on atrogene expression in quadriceps muscle. PKB activity, as assessed by Thr(308) and Ser(473) phosphorylation, was significantly higher ...

The protein TRB3 (tribbles 3), also called NIPK (neuronal cell death-inducible protein kinase), was recently identified as a protein-protein interaction partner and an inhibitor of PKB (protein kinase B). To explore the hypothesis that TRB3/NIPK might act as a negative regulator of insulin signalling in the liver, this protein was overexpressed by adenoviral transduction of primary cultures of ...

We investigated whether the effect of troglitazone on glucose disposal is associated with altered insulin signaling. Nondiabetic first-degree relatives of type 2 diabetic patients (age 30 +/- 2 years, BMI 30 +/- 1 kg/m(2); n = 20) were randomized in a double-blind manner to 3 months of troglitazone (200 mg/day) or placebo treatment. Before and after treatment, 3-h euglycemic-hyperinsulinemic gl...

Protein kinase B (PKB or Akt) is a mitogen-regulated protein kinase involved in the protection of cells from apoptosis, the promotion of cell proliferation and diverse metabolic responses [1]. Its activation is initiated by the binding of 3' phosphorylated phosphoinositide lipids to its pleckstrin homology (PH) domain, resulting in the induction of activating phosphorylation at residues Thr308 ...

The genetic manipulation of mice has become an essential and elegant method for studying the function of proteins in physiology, and for testing the veracity of information obtained from cell culture experiments. During the past few years, a variety of transgenic and knockout mouse models of PKB (protein kinase B)/Akt have been generated and investigated. In this paper, we focus on the phenotyp...

We have addressed the differential roles of class I Phosphoinositide 3-kinases (PI3K) in human breast-derived MCF10a (and iso-genetic derivatives) and MDA-MB 231 and 468 cells. Class I PI3Ks are heterodimers of p110 catalytic (α, β, δ and γ) and p50-101 regulatory subunits and make the signaling lipid, phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3) that can activate effectors, eg ...

The p53 protein is one of the major tumor suppressor proteins. In response to DNA damage, p53 is prevented from degradation and accumulates to high levels. Ionizing radiation leads to hypophosphorylation of the p53 ubiquitin ligase Mdm2 at sites where phosphorylation is critical for p53 degradation and to the phosphorylation and activation of Akt/PKB, a kinase that phosphorylates and inhibits G...

Leukemia inhibitory factor (LIF) is a member of interleukin-6 related cytokines, which induces cardiac hypertrophy through glycoprotein (gp) 130. In this study, the role of phosphatidylinositol (PI) 3-kinase, Akt/protein kinase B (Akt/PKB), and p70 S6 kinase activation in LIF-induced hypertrophic responses such as stimulation of protein synthesis, atrial natriuretic peptide (ANP) gene expressio...