We examined the mechanism of atrial natriuretic factor (ANF) transcription by isoproterenol (ISO), an agonist for the beta-adrenergic receptor (betaAR), in cardiac myocytes. ISO only modestly activated members of the mitogen-activated protein kinase family. ISO-induced ANF transcription was not affected by inhibition of mitogen-activated protein kinases, whereas it was significantly inhibited b...

Sphingosine kinase-1 (Sphk1) and its product, sphingosine-1-phosphate (S1P) are important regulators of cardiac growth function. Numerous studies have reported that Sphk1/S1P signaling is essential for embryonic development promotes pathological hypertrophy in adulthood. However, no addressed the role Sphk1 postnatal cardiomyocyte (CM) so far. The present study aimed to assess molecular mechani...

Dysregulation of post-translational modifications (PTMs) like phosphorylation is often involved in disease. NMR may elucidate exact loci and time courses PTMs at atomic resolution near-physiological conditions but requires signal assignment to individual atoms. Conventional methods for this base on tedious global that fail, as large intrinsically disordered proteins (IDPs). We present a sensiti...

DNA methyltransferase 1 (DNMT1) catalyzes DNA methylation and is overexpressed in many human diseases, including cancer. The tobacco-specific carcinogen NNK also induces DNA methylation. However, the role of DNMT1-mediated methylation in tobacco carcinogenesis remains unclear. Here we used human and mouse lung cancer samples and cell lines to determine a mechanism whereby NNK induced DNMT1 expr...

We characterized metabolic and mitogenic signaling pathways in isolated skeletal muscle from well-matched type 2 diabetic and control subjects. Time course studies of the insulin receptor, insulin receptor substrate (IRS)-1/2, and phosphatidylinositol (PI) 3-kinase revealed that signal transduction through this pathway was engaged between 4 and 40 min. Insulin-stimulated (0.6-60 nmol/l) tyrosin...

MITF (microphthalmia-associated transcription factor) is a basic-helix-loop-helix-leucine zipper (bHLHZip) factor which regulates expression of tyrosinase and other melanocytic genes via a CATGTG promoter sequence, and is involved in melanocyte differentiation. Mutations of MITF in mice or humans with Waardenburg syndrome type 2 (WS2) often severely disrupt the bHLHZip domain, suggesting the im...

Studies of rat skeletal glycogen metabolism carried out in a perfused hindlimb system indicated that epinephrine activates phosphorylase via the cascade of phosphorylation reactions classically linked to the beta-adrenergic receptor/adenylate cyclase system. The beta blocker propranolol completely blocked the effects of epinephrine on cAMP, cAMP-dependent protein kinase, phosphorylase, and gluc...

Purified preparations of rabbit skeletal muscle glycogen synthase (specific activity 6 to 42 units/mg of protein) were found to be contaminated with calciumdependent kinase(s) which catalyzed the phosphorylation of glycogen phosphorylase b and glycogen synthase. In a series of glycogen synthase preparations there was a correlation between the phosphorylation rates of glycogen synthase and of ad...

Incubation of isolated hepatocytes with glutamine or proline or in hypotonic media is known to activate glycogen synthase and acetyl-CoA carboxylase as a result of cell swelling. We report here that the same experimental conditions caused an activation of phosphatidylinositol 3-kinase and p70 ribosomal protein S6 kinase (p70 S6 kinase) but did not modify the activity of p42 mitogen-activated pr...