PTP-PEST controls motility through regulation of Rac1.

The cytoplasmic protein tyrosine phosphatase, PTP-PEST, associates with the focal adhesion proteins p130cas and paxillin and has recently been implicated in cell migration. In this study, we investigated the mechanism by which PTP-PEST regulates this phenomenon. We find that PTP-PEST is activated in an adhesion-dependent manner and localizes to the tips of membrane protrusions in spreading fibroblasts.

Activation of phospholipase C-epsilon by heterotrimeric G protein betagamma-subunits.

PLC-epsilon was identified recently as a phosphoinositide-hydrolyzing phospholipase C (PLC) containing catalytic domains (X, Y, and C2) common to all PLC isozymes as well as unique CDC25- and Ras-associating domains. Novel regulation of this PLC isozyme by the Ras oncoprotein and alpha-subunits (Galpha(12)) of heterotrimeric G proteins was illustrated. Sequence analyses of PLC-epsilon revealed previously unrecognized PH and EF-hand domains in the amino terminus.

Farnesyltransferase inhibitors: potential role in the treatment of cancer.

New targets for drug discovery have been identified rapidly as a result of the many recent and rapid advances in the understanding of signal transduction pathways that contribute to oncogenesis. In particular, oncogenic Ras proteins have been seen as an important target for novel anti-cancer drugs. Since the decade-old identification and cloning of farnesyltransferase (FTase), a critical enzyme that post-translationally modifies Ras and other farnesylated proteins, FTase inhibitors (FTIs) have been under intense investigation designed to bring them to clinical practice for cancer therapy.

Selective drug resistant human osteosarcoma cell lines.

Chemotherapy in combination with surgery has been shown to be effective for the control of osteosarcoma. Development of resistance to chemotherapeutic agents is a recurring clinical problem. To investigate this phenomena, human osteosarcoma cells, TE-85, were exposed to increasing doses of Taxol or Taxotere during a 9-month period.

Rit, a non-lipid-modified Ras-related protein, transforms NIH3T3 cells without activating the ERK, JNK, p38 MAPK or PI3K/Akt pathways.

The biological functions of Rit (Ras-like protein in tissues) and Rin (Ras-like protein in neurons), members of a novel branch of Ras-related GTP-binding proteins that are approximately 50% identical to Ras, have not been characterized. Therefore, we assessed their activity in growth control, transformation and signaling. NIH cells stably expressing a constitutively activated mutant of Rit [Rit(79L)] (analogous to the oncogenic mutant H-Ras(61L)) demonstrated strong growth transformation, proliferating rapidly in low serum and forming colonies in soft agar and tumors in nude mice.

Evaluation of 201T1 SPECT for predicting early treatment response in patients with squamous cell carcinoma of the extracranial head and neck treated with nonsurgical organ preservation therapy: initial results.

Purpose: The purpose of this work was to prospectively determine the ability of 210TI single photon emission CT (SPECT) to monitor treatment response in patients with head and neck squamous cell carcinoma (HNSCCA) treated with nonsurgical organ preservation.

Method: Nine patients with HNSCCA underwent 201T1 SPECT before and 6 weeks after completion of nonsurgical organ preservation therapy. All cases were evaluated for uptake at the primary site before and after treatment.

The A20 protein interacts with the Epstein-Barr virus latent membrane protein 1 (LMP1) and alters the LMP1/TRAF1/TRADD complex.

The Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) interacts with the tumor necrosis factor receptor (TNFR)-associated factor (TRAF) molecules, which are important for LMP1-mediated signaling. Two domains of LMP1 can independently activate NF-kB, carboxyl-terminal activating region 1 (CTAR1) and CTAR2. The activation of NF-kB by CTAR1 occurs through direct interaction of LMP1 with the TRAF molecules, whereas CTAR2 interacts with the TNFR-associated death domain protein (TRADD) to activate NF-kB and the c-Jun N-terminal kinase (JNK).

Thallium-201 single-photon emission CT versus CT for the detection of recurrent squamous cell carcinoma of the head and neck.

Background And Purpose: Thallium-201 single-photon emission computed tomography (SPECT) can be used to detect primary squamous cell carcinoma (SCCA) of the head and neck. Nevertheless, there have very few studies performed to evaluate the ability of thallium-201 to depict recurrent SCCA. The purpose of this study was to compare the ability of thallium-201 SPECT with CT to enable detection of recurrent SCCA of the upper aerodigestive tract.

Activity of recombinant HIV-1 integrase on mini-HIV DNA.

Integration of the human immunodeficiency virus type 1 (HIV-1) cDNA into the genome of a human cell is an essential step in the viral replication cycle. Understanding of the integration process has been facilitated by the development of in vitro assays using specific oligonucleotides and recombinant integrase. However, understanding of the biology of retroviral integration will require in vitro and in vivo model systems using long DNA substrates that mimic the HIV cDNA.

Epstein-Barr virus and human herpesvirus 8 prevalence in human immunodeficiency virus-associated oral mucosal lesions.

The prevalence of Epstein-Barr virus (EBV) and the recently identified Kaposi's sarcoma (KS)-associated herpesvirus (also designated human herpesvirus 8 [HHV-8]) was determined in oral lesions and oral neoplasms common to persons with human immunodeficiency virus (HIV) infection. Oral lesions were examined by polymerase chain reaction (PCR) for EBV and HHV-8 DNA and by Southern blot analysis for EBV clonality. EBV was detected by Southern blot in hairy leukoplakia lesions, in a subset of AIDS-related lymphomas, and in saliva from HIV-positive persons but not in pseudohairy leukoplakia lesions, oral aphthous ulcers, or oral KS lesions.

The intracellular IL-1 receptor antagonist alters IL-1-inducible gene expression without blocking exogenous signaling by IL-1 beta.

The epithelium-associated tissue distribution of the intracellular IL-1R antagonist (icIL-1Ra) suggests that it functions as a novel regulatory molecule for IL-1 in somatic tissues. We examined the role of the icIL-1Ra in IL-1 beta-induced responses in human ovarian cancer cells because ovarian surface epithelium expresses transcripts for the icIL-1Ra, and the majority of ovarian cancers arise from these cells. Several human ovarian and cervical cancer cell lines spontaneously express the icIL-1Ra.

Pyridine nucleotide redox potential modulates cystic fibrosis transmembrane conductance regulator Cl- conductance.

Cl- conductance of the apical membrane of airway epithelial cells has properties of a passive diffusion mechanism but is decreased by inhibition of oxidative metabolism. Recent reports that cAMP-dependent Cl- conductance also requires ATP at the intracellular domains of the cystic fibrosis transmembrane conductance regulator (CFTR) suggests that ATP concentration could mediate metabolic regulation of Cl- conductance. However, metabolic inhibitors affect processes other than ATP free energy levels, including notably the metabolic pathways that set the redox potential of pyridine nucleotides within the cell.

Ras (CXXX) and Rab (CC/CXC) prenylation signal sequences are unique and functionally distinct.

Rab proteins typically lack the consensus carboxyl-terminal CXXX motif that signals isoprenoid modification of Ras and other isoprenylated proteins and, instead, terminate in either CC or CXC sequences (C = cysteine, X = any amino acid). To compare the functional relationship between the Ras CXXX and the Rab CC/CXC motifs, we have generated chimeric Ras proteins terminating in Rab carboxyl-terminal CC or CXC sequences. These mutant Ras proteins were not isoprenylated in vitro or in vivo, demonstrating that the CC and CXC sequences alone are not sufficient to replace a CXXX sequence to signal Ras isoprenoid modification.

Differential suppression of interferon-gamma-induced Ia antigen expression on cultured rat astroglia and microglia by second messengers.

The roles of intracellular second messengers in interferon-gamma (IFN-gamma)-induced Ia antigen (Ag) expression by astroglia and microglia were examined. Ia Ag on both glia types was induced by IFN-gamma. Reagents known to increase intracellular cAMP or activate intracellular protein kinase C (PKC) reduced IFN-gamma-induced Ia Ag expression by astroglia.

Comparison and quantitation of Ia antigen expression on cultured macroglia and ameboid microglia from Lewis rat cerebral cortex: analyses and implications.

We isolated two subclasses of astrocytes, oligodendrocytes and ameboid microglia from Lewis rat cerebral cortex and analyzed Ia antigen expression on each glial cell type by immunofluorescent microscopy and cytofluorometry. All of these expressed little or no Ia without interferon-gamma (IFN-gamma) treatment. Following IFN-gamma treatment, Ia expression was observed on a majority (approximately 80%) of ameboid microglia, on half (approximately 55%) of the type 1 astrocytes, on a small number (approximately 7%) of type 2 astrocytes, but not on oligodendrocytes.

Expression of ras proto-oncogenes in the Dunning R3327 rat prostatic adenocarcinoma system.

Steady-state levels of c-Ha-ras mRNA were measured in eight sublines of the Dunning R3327 rat prostatic adenocarcinoma. As a control, normal dorsal prostate tissue was studied. Increased expression of c-Ha-ras is associated with tumor progression in one lineage of the Dunning R3327 system (H to AT1 to MAT-Lu and MAT-Ly-Lu).