SHIP is a 145-kD SH 2-containing i nositol-5- p hosphatase widely expressed in hemopoietic cells. It was first identified as tyrosine phosphoprotein associated with Shc response to numerous cytokines. has been implicated FcγRIIB receptor-mediated negative signaling B cells and mast postulated down-regulate cytokine signal transduction myeloid To define further its role the proliferation differentiation of progenitors, well function mature cells, we have generated embryonic stem mice bearing...

Growth and differentiation of thymocytes mature T lymphocytes is regulated by cellular interactions that are in part mediated soluble factors. We identify IL-6, formerly called B cell stimulating factor (BSF-2). IFN-beta 2, or hybridoma-plasmacytoma growth (HPGF) as a novel costimulant rIL-6 induced six-to seven-fold increase proliferation human stimulated with suboptimal doses PHA. A similar effect added IL-6 could be observed using peripheral blood lymphocytes, but only if the cultures...

Abstract The interaction between human endothelial cells and leukocytes during immunologic inflammatory responses is in part mediated through the release of soluble mediators. We report that cultured umbilical vein secrete IL-6 when stimulated with LPS. This effect was inhibited by polymyxin-B. monokines IL-1 TNF-alpha were also potent inducers IL-6, whereas lymphotoxin only effective at much higher concentrations. Endothelial cell supernatant active as hybridoma-plasmacytoma growth factor...

Entry of human immunodeficiency virus type 1 (HIV-1) into cells requires binding to CD4 and fusion with a cellular membrane. Fusion does not occur in most nonhuman even when they express CD4, indicating that one or more accessory factors are required for infection. Recently, seven-transmembrane domain protein has been shown serve as an factor T-cell-tropic (T-tropic) HIV-1 isolates (Y. Feng, C. Broder, P. E. Kennedy, A. Berger, Science 272:872-877, 1996). Here we show expression this...

It is well established that misfolded forms of cellular prion protein (PrP [PrPC]) are crucial in the genesis and progression transmissible spongiform encephalitis, whereas function native PrPC remains incompletely understood. To determine physiological role PrPC, we examine neurophysiological properties hippocampal neurons isolated from PrP-null mice. We show mouse exhibit enhanced drastically prolonged N-methyl-d-aspartate (NMDA)–evoked currents as a result functional upregulation NMDA...

The intracellular domain of human protein tyrosine phosphatase beta (HPTP beta) (44 kDa) was expressed in bacteria, purified using epitope 'tagging' immunoaffinity chromatography, and characterized with respect to kinetic profile, substrate specificity potential modulators enzyme activity. A chromogenic assay based on the Malachite Green method employed for detection inorganic phosphate (Pi) released from phosphopeptides by HPTP beta. This assay, modified so as improve its sensitivity,...

SUMMARY Understanding the developmental and genetic basis for evolutionarily significant morphological variation in complex phenotypes such as mammalian skull is a challenge because of sheer complexity factors involved. We hypothesize that even this system, expression phenotypic structured by interaction few key processes. To test hypothesis, we created highly variable sample crania using four mouse mutants their wild‐type controls from similar backgrounds with perturbations to particular...

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models humans. Tex characterized by progressive loss of effector functions, high sustained inhibitory receptor expression, ...Read More

The vascular disrupting agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a murine agonist of the stimulator interferon genes (STING), appears to target tumor vasculature primarily as result stimulating pro-inflammatory cytokine production from tumor-associated macrophages (TAMs). Since there were relatively few reports DMXAA effects in genetically-engineered mutant mice (GEMM), and models non-small cell lung cancer (NSCLC) particular, we examined both effectiveness macrophage dependence...

Lysyl oxidase (LOX), an extracellular matrix remodeling enzyme, appears to have a role in promoting breast cancer cell motility and invasiveness. In addition, increased LOX expression has been correlated with decreases both metastases-free, overall survival patients. With this background, we studied the ability of beta-aminopropionitrile (BAPN), irreversible inhibitor LOX, regulate metastatic colonization potential human line, MDA-MB-231. BAPN was administered daily mice starting either 1...

Supramolecular complexes of a family positively charged conjugated polymers (CPs) and green fluorescent protein (GFP) create fluorescence resonance energy transfer (FRET)-based ratiometric biosensor array. Selective multivalent interactions the CPs with mammalian cell surfaces caused differential change in FRET signals, providing fingerprint signature for each type. The resulting signatures allowed identification 16 different types discrimination between healthy, cancerous, metastatic cells,...

Rapid and sensitive methods of discriminating between healthy tissue metastases are critical for predicting disease course designing therapeutic strategies. We report here the use an array gold nanoparticle-green fluorescent protein elements to rapidly detect metastatic cancer cells (in minutes), as well discriminate organ-specific their corresponding normal tissues through overall intracellular proteome signatures. Metastases established in a new preclinical non-small-cell lung metastasis...

Abstract Detection of cytoplasmic DNA by the host’s innate immune system is essential for microbial and endogenous pathogen recognition. In mammalian cells, an important sensor stimulator interferon genes (STING) protein, which upon activation bacterially-derived cyclic dinucleotides (cDNs) or cytosolic dsDNA (dsDNA), triggers type I interferons pro-inflammatory cytokine production. Given abundance cDNs in gut, we determined whether STING deletion, stimulation, acts to modulate severity...

Abstract Pituitary adenylate cyclase-activating polypeptide (PACAP) is a hormone belonging to the glucagon superfamily of hormones. These hormones are known play important roles in metabolism and growth. PACAP neuropeptide that causes accumulation cAMP number tissues affects secretion other hormones, vasodilation, neural immune functions, as well cell cycle. To determine whether essential for survival evaluate its function(s), we have generated mice lacking gene via homologous recombination....

The tight-skin ( Tsk /+) mutant mouse, a putative murine model of scleroderma, is characterized primarily by the excessive deposition collagen and other extracellular matrix molecules in dermis, also developmentally acquired defect pulmonary architecture. Passive transfer experiments have suggested an etiologic role for immune system /+ dermal pathology. In addition, CD4+ T lymphocytes been shown to be required accumulation these mice. As IL-4, product differentiated cells, capable...

Binding of interleukin (IL)-3 and granulocyte/macrophage colony-stimulating factor (GM-CSF) to their high affinity cell surface receptors induces tyrosine phosphorylation a similar set protein substrates. We have identified one these common substrates (p70) as the protein-tyrosine phosphatase SHPTP2. The Src homology 2 (SH2) domain adaptor Grb2 bound with tyrosine-phosphorylated SHPTP2 following treatment cells IL-3 or GM-CSF, but not IL-4. This interaction was inhibited by two...

Transgenic mouse lineages were established that carry the normal (M) or mutant (Z) alleles of human α 1 -antitrypsin (α -Pi) gene. All -Pi transgenic mice expressed protein in liver, cartilage, gut, kidneys, lymphoid macrophages, and thymus. The M-allele was secreted normally into serum. However, Z-allele accumulated several cell types, but particularly hepatocytes, found serum tenfold lower concentrations than protein. Mice one lineage carrying Z allele high levels RNA displayed significant...

Rheumatoid arthritis, a debilitating, systemic inflammatory joint disease, is likely accompanied by alterations in circulating metabolites. Here, an 1H NMR spectroscopy-based metabolomics approach was developed to establish metabolic 'biomarker pattern' model of rheumatoid the K/BxN transgenic mouse. Sera obtained from arthritic mice (N = 15) and control population 19) having same genetic background, but lacking arthritogenic T-cell receptor KRN transgene, were compared spectroscopy. A...

The roles of protein-tyrosine phosphatases (PTPs) in processes such as cell growth and adhesion are poorly understood. To explore the ability specific PTPs to regulate signaling pathways initiated by stimulation factor receptors, we expressed receptor-like PTP, PTPα, A431 epidermoid carcinoma cells. These cells express high levels epidermal (EGF) receptor proliferate response autocrine production transforming factor-α. Conversely, EGF <i>in vitro</i> leads inhibition triggers rapid...

In this study we have investigated the role that Src homology 2 domain (SH2) of 145-kDa 5-phosphatase, SH2-containing inositol phosphatase (SHIP), plays in three properties been associated with protein following cytokine stimulation: its association Shc, tyrosine phosphorylation, and inhibition hemopoietic cell growth. vitro studies using SH2 revealed it was capable binding directly to Tyr(P)317 motif Shc a KD approximately 290 nM, keeping other specific SH2/Tyr(P) interactions. vivo...

Kashin-Beck disease, a syndrome characterized by short stature, skeletal deformities, and arthropathy of multiple joints, is highly prevalent in specific regions Asia. The disease has been postulated to result from combination different environmental factors, including contamination barley mold mycotoxins, iodine deficiency, presence humic substances drinking water, and, importantly, deficiency selenium. This multifunctional trace element, the form selenocysteine, essential for normal...

Abstract To study the role of Pten tumor suppressor in skeletogenesis, we generated mice lacking this key phosphatidylinositol 3′-kinase pathway regulator their osteo-chondroprogenitors. A phenotype growth plate dysfunction and skeletal overgrowth was observed. Introduction: Skeletogenesis is a complex process relying on variety ligands that activate range intracellular signal transduction pathways. Although many these stimuli are known to (PI3K), function during cartilage development...