نتایج جستجو برای: مسیر ras

تعداد نتایج: 54191  

Journal: :Proceedings of the National Academy of Sciences of the United States of America 1995
J S Scheele J M Rhee G R Boss

We devised enzyme-based methods to measure fmol amounts of GDP and GTP and applied these methods to measure absolute amounts of Ras-bound GDP and GTP in NIH 3T3 fibroblasts. We found that parental NIH 3T3 cells contained 509 and 1.3 fmol of Ras-bound GDP and GTP, respectively, per mg of cellular protein and that stable transfectants of NIH 3T3 cells overexpressing wild-type Ha-Ras contained 700...

Journal: :The Journal of Experimental Medicine 1993
J Skipper H J Stauss

We have investigated the possibility of inducing cytotoxic T lymphocytes (CTL) to Ras containing a mutation at position 61 or to normal Ras, using recombinant vaccinia viruses expressing these proteins. CTL from C57Bl/10 mice immunized with vaccinia expressing mutant Ras showed specificity for the mutant Ras protein and recognition of normal Ras was inefficient. The opposite specificity was obs...

Journal: :Cancer research 2004
Lynn B Eckert Gretchen A Repasky Aylin S Ulkü Aidan McFall Hong Zhou Carolyn I Sartor Channing J Der

Although mutated forms of ras are not associated with the majority of breast cancers (<5%), there is considerable experimental evidence that hyperactive Ras can promote breast cancer growth and development. Therefore, we determined whether Ras and Ras-responsive signaling pathways were activated persistently in nine widely studied human breast cancer cell lines. Although only two of the lines h...

2017
Mark Kerstjens Emma M.C. Driessen Merel Willekes Sandra S. Pinhanços Pauline Schneider Rob Pieters Ronald W. Stam

Acute lymphoblastic leukemia (ALL) in infants is an aggressive malignancy with a poor clinical outcome, and is characterized by translocations of the Mixed Lineage Leukemia (MLL) gene. Previously, we identified RAS mutations in 14-24% of infant ALL patients, and showed that the presence of a RAS mutation decreased the survival chances even further. We hypothesized that targeting the RAS signali...

Journal: :The Journal of biological chemistry 1998
A B Vojtek C J Der

Ras is a key regulator of cell growth in all eukaryotic cells. Genetic, biochemical, and molecular studies in Caenorhabditis elegans, Drosophila, and mammalian cells have positioned Ras centrally in signal transduction pathways that respond to diverse extracellular stimuli, including peptide growth factors, cytokines, and hormones. The biological activity of Ras is controlled by a regulated GDP...

Journal: :Molecular and cellular biology 1996
R Khosravi-Far M A White J K Westwick P A Solski M Chrzanowska-Wodnicka L Van Aelst M H Wigler C J Der

Substantial evidence supports a critical role for the activation of the Raf-1/MEK/mitogen-activated protein kinase pathway in oncogenic Ras-mediated transformation. For example, dominant negative mutants of Raf-1, MEK, and mitogen-activated protein kinase all inhibit Ras transformation. Furthermore, the observation that plasma membrane-localized Raf-1 exhibits the same transforming potency as o...

Journal: :Cell 2004
Holger Sondermann Stephen M. Soisson Sean Boykevisch Shao-Song Yang Dafna Bar-Sagi John Kuriyan

The classical model for the activation of the nucleotide exchange factor Son of sevenless (SOS) involves its recruitment to the membrane, where it engages Ras. The recent discovery that Ras*GTP is an allosteric activator of SOS indicated that the regulation of SOS is more complex than originally envisaged. We now present crystallographic and biochemical analyses of a construct of SOS that conta...

Journal: :Proceedings of the National Academy of Sciences of the United States of America 2012
Till Maurer Lindsay S Garrenton Angela Oh Keith Pitts Daniel J Anderson Nicholas J Skelton Benjamin P Fauber Borlan Pan Shiva Malek David Stokoe Mary J C Ludlam Krista K Bowman Jiansheng Wu Anthony M Giannetti Melissa A Starovasnik Ira Mellman Peter K Jackson Joachim Rudolph Weiru Wang Guowei Fang

The Ras gene is frequently mutated in cancer, and mutant Ras drives tumorigenesis. Although Ras is a central oncogene, small molecules that bind to Ras in a well-defined manner and exert inhibitory effects have not been uncovered to date. Through an NMR-based fragment screen, we identified a group of small molecules that all bind to a common site on Ras. High-resolution cocrystal structures del...

Journal: :Molecular cell 2011
David Matallanas David Romano Fahd Al-Mulla Eric O'Neill Waleed Al-Ali Piero Crespo Brendan Doyle Colin Nixon Owen Sansom Matthias Drosten Mariano Barbacid Walter Kolch

K-Ras mutations are frequent in colorectal cancer (CRC), albeit K-Ras is the only Ras isoform that can elicit apoptosis. Here, we show that mutant K-Ras directly binds to the tumor suppressor RASSF1A to activate the apoptotic MST2-LATS1 pathway. In this pathway LATS1 binds to and sequesters the ubiquitin ligase Mdm2 causing stabilization of the tumor suppressor p53 and apoptosis. However, mutan...

Journal: :Molecular and cellular biology 2014
Yong Zhou Hong Liang Travis Rodkey Nicholas Ariotti Robert G Parton John F Hancock

Lipid-anchored Ras GTPases form transient, spatially segregated nanoclusters on the plasma membrane that are essential for high-fidelity signal transmission. The lipid composition of Ras nanoclusters, however, has not previously been investigated. High-resolution spatial mapping shows that different Ras nanoclusters have distinct lipid compositions, indicating that Ras proteins engage in isofor...

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