Twelve peroxovanadium (pV) compounds, each containing an oxo ligand, one or two peroxo anions, and ancillary ligand in the inner coordination sphere of V, were synthesized, crystallized, characterized by 51V NMR as > 95% pure. These compounds activated insulin receptor kinase (IRK) cultured hepatoma cells, stimulated lipogenesis adipocytes, inhibited situ dephosphorylation autophosphorylated IRs epidermal growth factor receptors rat liver endosomes. The phosphotyrosine phosphatase inhibitory...

We investigated the metabolic fate of a low dose (25 micro g/kg) bisphenol A [2,2-bis(4-hydroxy-phenyl)propane] (BPA) injected subcutaneously in CD1 pregnant mice using tritium-labeled molecule. Analytic methods were developed to allow radio-chromatographic profiling BPA residues excreta and tissues, as well mothers' reproductive tracts fetuses, that contained more than 4% administered radioactivity. was extensively metabolized by mice. Identified metabolite structures included glucuronic...

Leishmania-induced macrophage (Mϕ) dysfunctions have been correlated with altered signaling events. Recent findings from our laboratory suggest that modulation of host protein tyrosine phosphatase (PTP) following Leishmania infection could lead to these Mϕ defects. To address this issue, PTP activity and IFN-γ-inducible events were evaluated in donovani (Ld)-infected cells. We observed Ld promastigotes can rapidly trigger simultaneously dephosphorylation tyrosyl residues inhibition kinase...

The autophosphorylation, from [gamma-32P]ATP, of insulin and epidermal growth factor receptors in rat liver endosomes peaked at 2-5 min declined thereafter. When autophosphorylation either [gamma-32P]ATP or unlabeled ATP was stopped after 5 by adding excess EDTA +/- ATP, the phosphotyrosine (PY) content each receptor decreased 37 degrees C with a t 1/2 1.6 min. This equally so whether PY 32P-labeled analyzed autoradiography KOH-treated gels Western blotting antibodies immunoprecipitated...

Phagocyte functions are markedly inhibited after infection with the intracellular protozoan parasiteLeishmania. This situation strongly favors installation and propagation of this pathogen within its mammalian host. Previous findings by us others have established that alteration several signaling pathways (protein kinase C-, Ca2+- protein-tyrosine kinases-dependent events) were directly responsible for Leishmania-induced macrophage (MØ) dysfunctions. Here we report modulation...

Replication of human immunodeficiency virus type 1 (HIV-1) is increased by different cytokines and T cell activators, also known to modulate tyrosine phosphorylation levels. A novel class protein phosphatase (PTP) inhibitors, peroxovanadium (pV) compounds, were tested for a putative effect on HIV-1 long terminal repeat (LTR) activity. We found that these PTP inhibitors markedly enhanced LTR activity in 1G5 cells, stably transfected line harbors an LTR-driven luciferase construct. direct...

Abstract The addition of the peroxovanadium (pV) derivatives potassium bisperoxo(1,10‐phenanthroline)oxovanadate(v) (bpV[phen]) or bisperoxo(pyridine‐2‐carboxylato)oxovanadate(v) (bpV[pic]), both which are potent inhibitors protein tyrosine phosphatases (PTPs) [Posner et al. (1994): J Biol Chem 269:4596–4604], to culture medium neuroblastoma NB 41 and glioma C6 cells resulted in a marked decrease their proliferation rates progressive accumulation at G2/M transition cell cycle. effect was...

The phosphotyrosine phosphatase inhibitor bpV(phen) has the ability to markedly decrease progression of leishmaniasis in vivo. Here, we have identified mechanisms that are responsible for this protective effect. We report two potent peroxovanadium (pV) compounds, and bpV(pic), control a similar manner by modulating NO-dependent microbicidal action. observed their injection can rapidly transiently induce expression inducible NO synthase (iNOS) livers mice enhance circulating nitrate levels....

Numerous sperm proteins have been identified on the basis of their increase in tyrosine phosphorylation during capacitation. However, kinases present spermatozoa that are responsible for this remain unknown. As devoid transcriptional and translational activities, molecular biology approaches might not reflect pattern mature spermatozoa. Working directly with ejaculated is most reliable approach to identify potentially involved capacitation-associated protein phosphorylation. A combination...

Insulin is internalized with its cognate receptor into the endosomal apparatus rapidly after binding to hepatocytes. We performed a bioinformatic screen of Golgi/endosome hepatic protein fractions and found that ATIC, which rate-limiting enzyme in de novo purine biosynthesis pathway, PTPLAD1 are associated insulin (IR) internalization. The IR interactome (IRGEN) connects ATIC AMPK within network (GEN). Forty-five percent have common heritable variants type 2 diabetes, including AMPK. show...

Mouse prostate membrane-associated proteins of the annexin family showed changes in SUMOylation during androgen treatment. Among these calcium-binding A1 protein (ANXA1) was chosen for further characterization given its role secretion and cancer. ANXA1 confirmed by overexpressing SUMO-1 LNCaP cells. Site-directed mutagenesis indicated that K257 located a consensus motif C-terminal DA3 repeat domain is SUMOylated. Mutation N-terminal Y21 decreased markedly signal while EGF stimulation...

Polypeptide hormone signal transmission by receptor tyrosine kinases requires the rapid reversal of phosphorylation protein phosphotyrosine phosphatases (PPTPases). We studied hepatic PPTPases in rat with emphasis on acute and chronic regulation insulin. PPTPase activity artificial substrates ([32P]Tyr-reduced, carboxyamidomethylated, maleylated lysozyme [32P]Tyr-poly[glutamic acid:tyrosine] 4:1) was present distinct membrane, cytoskeletal, cytosolic fractions. These activities were...

The nuclear T3 receptor (NTR) was affinity-labeled with bromoacetyl-[125I]T3, purified by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and used to immunize BALB/c mice. Spleen cells from one strongly immunoreactive mouse were fused Sp2 myeloma cells, 328 hybridomas screened a dot-blot immunoassay using as antigen, preparation of NTR partially diethylaminoethyl-Sephadex chromatography. Four positive cultures thus found; three which confirmed comparing Western...

Mutations in the EIF2AK3 gene have been identified patients with Wolcott-Rallison syndrome - a rare autosomal recessive disorder associated permanent neonatal insulin-dependent diabetes. Despite fact that different mutations observed every single unrelated case reported so far, most presented similar characteristics, such as osteopenia, epiphyseal dysplasia well hepatic and/or renal dysfunction. The was analyzed using PCR-based sequencing approach two and their parents. We report cases from...

Insulin receptor (IR) endocytosis requires a remodelling of the actin cytoskeleton. We show here that ANXA2 is SUMOylated at K10 located in non‐consensus SUMOylation motif N‐terminal domain. The Y24F mutation decreased signal, whereas insulin stimulation increased SUMOylation. A survey protein hepatic Golgi/endosome (G/E) fractions after injections revealed presence pattern and confirmed ANXA2. construction an IR/ANXA2/SUMO network (IRASGEN) G/E context reveals interacting nodes whereby...

A proteomic analysis of stratum corneum (SC) samples normal healthy skin revealed the presence more than 70 proteins by 2D electrophoresis. The majority these to our knowledge have not yet been described in SC. We analysed Western blot levels 25 SC taken from postmenopausal and dry compared with young skin, respectively. In there was a significantly increased amount heat shock protein 27, plakoglobin desmoglein 1, whereas transglutaminase 3, apolipoprotein D acid ceramidase were reduced...

The treatment of pediatric low-grade gliomas with current modalities still remains ineffective among a subset patients; hence, justifying the need to further investigate more effective therapies. Dipotassium bisperoxo (picolinato) oxovanadate V (Bpv[pic]), is derivative trace metal vanadium and potent inhibitor protein tyrosine phosphatases, which are important mediators oncogenic tumor suppressive activities in cancers. In this study, we undertook preclinical evaluation antineoplastic...