We previously established that overexpression of the EGF receptor (EGFR) is sufficient to induce tumor formation by otherwise nontransformed mammary epithelial cells, and initiation epithelial-mesenchymal transition (EMT) capable increasing invasion metastasis these cells. Using this breast cancer (BC) model, we find in addition EGF, adhesion fibronectin (FN) activates signal transducer activator transcription 3 (STAT3) through EGFR-dependent -independent mechanisms. Importantly, EMT...

Toxoplasma gondii resides in an intracellular compartment (parasitophorous vacuole) that excludes transmembrane molecules required for endosome-lysosome recruitment. Thus, the parasite survives by avoiding lysosomal degradation. However, autophagy can re-route parasitophorous vacuole to lysosomes and cause killing. This raises possibility T. may deploy a strategy prevent autophagic targeting maintain non-fusogenic nature of vacuole. We report activated EGFR endothelial cells, retinal pigment...

Abstract Aseptic loosening is thought to be due primarily osteolysis induced by cytokines and prostaglandins that are produced in response implant‐derived wear particles. Because endotoxin has many of the same effects as have been reported for particles, we hypothesized adherent may responsible biological responses We demonstrated presence significant levels on commonly used preparations titanium particles well titanium‐alloy implant surfaces. In contrast, supernatants obtained...

α-Tocopherol (vitamin E) is an essential nutrient for all vertebrates. From the eight naturally occurring members of vitamin E family, α-tocopherol most biologically active species and selectively retained in tissues. The hepatic transfer protein (TTP) preferentially selects dietary facilitates its transport through hepatocyte secretion to circulation. In doing so, TTP regulates body-wide levels α-tocopherol. mechanisms by which trafficking hepatocytes are poorly understood. We found that...

Ligand binding causes the epidermal growth factor (EGF) receptor to undergo accelerated internalization with eventual degradation in lysosomes. The goal of this study was investigate molecular basis endocytic sorting, focussing on post-internalization events. We have identified a sequence located between amino acid residues 675 and 697, encompassing dileucine motif at 679 680, that enhances endosome-to-lysosome transport when conformational restraints EGF carboxyl terminus are removed by...

Numerous studies by our lab and others demonstrate that epidermal growth factor receptor (EGFR) plays critical roles in primary breast cancer (BC) initiation, dissemination. However, clinical trials targeting EGFR function BC have lead to disappointing results. In the current study we sought identify mechanisms responsible for this disparity investigating of across continuum metastatic cascade. We previously established overexpression is sufficient formation situ tumors otherwise...

Abstract Therapeutic targeting of angiogenesis in glioblastoma has yielded mixed outcomes. Investigation tumor-associated focused on the factors that stimulate sprouting, migration, and hyperproliferation endothelial cells. However, little is known regarding processes underlying formation vessels. To address this issue, we investigated vessel CD31 + cells isolated from human tumors. The results indicate overexpression integrin α3β1 plays a central role promotion tube glioblastoma. Blocking...

The epidermal growth factor (EGF) receptor is located predominantly in the basolateral membrane of polarized epithelia, where it plays a pivotal role during organogenesis and tissue homeostasis. We have shown previously that 22-amino acid sequence EGF juxtamembrane domain contains autonomous sorting information necessary for localization using Madin-Darby canine kidney epithelial cell model. goal this study was to determine molecular basis expression site-directed mutagenesis modify specific...

Expression of the epidermal growth factor (EGF) was analyzed in six human hepatocellular carcinoma-derived and one hepatoblastoma-derived cell line, each which retained differentiated phenotype functions parenchymal hepatocyte. The level receptor expression hepatoma line similar to that normal fibroblast, approximately 10(5) molecules per cell. However, NPLC/PRF/5, a subline PLC/PRF/5 obtained following reestablishment xenograft tumor vitro, found express 4 x 10(6) high-affinity EGF...

A 165-kilodalton (kDal) surface glycoprotein encoded by human chromosome 7 (SA-7) had been characterized using antisera raised against 7-containing somatic cell hybrids. We now present evidence that SA-7 is the receptor for epidermal growth factor (EGF) and these recognize human-specific determinants. The gene coding EGF localized to p12 p22 region of 7. have 145-kDal/165-kDal doublet A431 cells after immunoprecipitation radiolabeled extracts with antisera. find a protein endogenous kinase...

Niemann-Pick disease type C (NPC) is caused by mutations in NPC1 or NPC2, which coordinate egress of low-density-lipoprotein (LDL)-cholesterol from late endosomes. We previously reported that the adenovirus-encoded protein RIDα rescues cholesterol storage phenotype NPC1-mutant fibroblasts. show here reconstitutes deficient endosome-to-endoplasmic reticulum (ER) transport, allowing excess LDL-cholesterol to be esterified acyl-CoA:cholesterol acyltransferase and stored lipid droplets (LDs)...

Human adenoviruses (Ads) generally cause mild self-limiting infections but can lead to serious disease and even be fatal in high-risk individuals, underscoring the importance of understanding how virus counteracts host defense mechanisms. This study had two goals. First, we wished determine molecular basis cholesterol homeostatic responses induced by early region 3 membrane protein RIDα via its direct interaction with sterol-binding ORP1L, a member evolutionarily conserved family...

ABSTRACT This manuscript describes a novel unconventional secretory pathway that facilitates EGF receptor (EGFR) signaling from apical membranes in polarized epithelial cells responding to immune cell mediators. Epithelial tissues provide physical barrier between our bodies and the external environment share an intimate relationship with circulating local cells. Our studies describe unexpected connection proinflammatory cytokine tumor necrosis factor‐alpha (TNF‐α) EGFR typically localized...

Dileucine-based motifs have been shown to regulate endosomal sorting of a number membrane proteins. Previously, we that the dileucine motif Leu679, Leu680 in juxtamembrane domain human epidermal growth factor receptor is involved endosome-to-lysosome transport ligand-receptor complexes. Substitution alanine residues for led reduction ligand-induced degradation without affecting internalization. In current study, further characterized ligand-dependent intracellular EGF receptors containing...

The epidermal growth factor receptor (EGFR) is localized at the basolateral membrane of most epithelial cells <i>in vivo</i> and in cell lines used to study protein sorting. goal this was define molecular basis polar EGFR expression using Madin-Darby canine kidney model. We have identified a 23-amino acid segment located near cytoplasmic face spanning domain (residues Lys-652 Ala-674) that necessary sufficient for targeting EGFRs from <i>trans</i>-Golgi network directly plasma membrane....

Previous studies with adenovirus mutants have indicated that a 10,400-molecular-weight (10.4K) protein predicted to be coded by an open reading frame in region E3 of functions down regulate the epidermal growth factor receptor (C. R. Carlin, A. E. Tollefson, H. Brady, B. L. Hoffman, and W. S. M. Wold, Cell 57:135-144, 1989). We now demonstrate 10.4K is fact synthesized cells infected group C adenoviruses. This was done immunoprecipitation from variety mutants, using antisera against three...

The main feature of polycystic kidney diseases (PKD) is formation and progressive enlargement renal cysts. Alterations in epithelial cell proliferation, extracellular matrix, ion transport are thought to contribute cyst loss function. Abnormal Cl- secretion implicated autosomal dominant PKD (ADPKD), but little known about abnormalities recessive (ARPKD). We developed a method isolate collecting duct (CD) principal cells (site the lesion ARPKD) from normal ARPKD mice. A transgenic mouse...

Using human-specific antibody reagents, we have examined the biosynthesis of epidermal growth factor receptor in human epidermoid carcinoma-derived A431 cells. Four Mr species (Mr = 70,000, 95,000, 135,000, and 145,000) are detected when cells subjected to a brief pulse L-[35S]methionine; an 165,000 is after 45-60 min exposure radiolabel. In pulse-chase experiments, four lower appear bear precursor relation protein. The molecule acquires N-linked oligosaccharide cotranslationally, two 95,000...

Human adenoviruses typically cause mild infections in the upper or lower respiratory tract, gastrointestinal ocular epithelium. However, may be life-threatening patients with impaired immunity and some serotypes epidemic outbreaks. Attachment to host cell receptors activates signaling virus uptake by endocytosis. At present, it is unclear how vital cellular homeostatic mechanisms affect these early steps adenovirus life cycle. Autophagy a lysosomal degradation pathway for recycling...