Research Topics
Genomes and Genes
| Channing DerSummaryAffiliation: University of North Carolina Country: USA Publications
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Publications
The RalB small GTPase mediates formation of invadopodia through a GTPase-activating protein-independent function of the RalBP1/RLIP76 effectorNicole F Neel
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Mol Cell Biol 32:1374-86. 2012..Instead, disruption of the ATPase function of RalBP1 impaired invadopodium formation. Our results identify a novel RalB-mediated biochemical and signaling mechanism for invadopodium formation...- Genetic and functional characterization of putative Ras/Raf interaction inhibitors in C. elegans and mammalian cellsVanessa González-Pérez
Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
J Mol Signal 5:2. 2010.... - Romidepsin inhibits Ras-dependent growth transformation of NIH 3T3 fibroblasts and RIE-1 epithelial cells independently of Ras signaling inhibitionAriella B Hanker
Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
J Mol Signal 4:5. 2009..These studies suggest that mutational activation of Ras may be a useful biomarker for sensitivity to romidepsin and that the anti-tumor activity of this HDAC inhibitor may involve inhibition of Ras effector-mediated signaling... 
Stopping ras in its tracksChanning J Der
Department of Pharmacology, University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, Chapel Hill, NC 27599, USA
Cell 129:855-7. 2007..This result will stimulate re-evaluation of pharmacological approaches to target Ras for cancer treatment...- Vav transformation requires activation of multiple GTPases and regulation of gene expressionTodd R Palmby
Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, CB 7295, Chapel Hill, NC 27599 7295, USA
Mol Cancer Res 2:702-11. 2004.... - Structural basis for the selective activation of Rho GTPases by Dbl exchange factorsJason T Snyder
Department of Biochemistry and Biophysics, Program in Molecular and Cellular Biophysics, Chapel Hill, North Carolina 27599, USA
Nat Struct Biol 9:468-75. 2002.... - Transforming activity of the Rho family GTPase, Wrch-1, a Wnt-regulated Cdc42 homolog, is dependent on a novel carboxyl-terminal palmitoylation motifAnastacia C Berzat
Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, 27599 7512, USA
J Biol Chem 280:33055-65. 2005..These results suggest that Wrch-1 membrane association, subcellular localization, and biological activity are mediated by a novel membrane-targeting mechanism distinct from that of Cdc42 and other isoprenylated Rho family GTPases... - p68RacGAP is a novel GTPase-activating protein that interacts with vascular endothelial zinc finger-1 and modulates endothelial cell capillary formationJulius Aitsebaomo
Carolina Cardiovascular Biology Center, The Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA
J Biol Chem 279:17963-72. 2004.... - Critical role of the pleckstrin homology and cysteine-rich domains in Vav signaling and transforming activityTodd R Palmby
Department of Pharmacology, University of North Carolina at Chapel Hill School of Medicine, Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina 27599 7295, USA
J Biol Chem 277:39350-9. 2002..Finally, we found that phosphatidylinositol 3-kinase activation may promote Vav membrane association via phosphatidylinositol 3,4,5-triphosphate binding to the PH domain... - Ras-mediated loss of the pro-apoptotic response protein Par-4 is mediated by DNA hypermethylation through Raf-independent and Raf-dependent signaling cascades in epithelial cellsKevin Pruitt
Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, 27599 7295, USA
J Biol Chem 280:23363-70. 2005.... - Essential role of Raf in Ras transformation and deregulation of matrix metalloproteinase expression in ovarian epithelial cellsAylin S Ulku
Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7295, USA
Mol Cancer Res 1:1077-88. 2003..In summary, in contrast to other epithelial cell types, Raf is a major effector for Ras transformation of ovarian epithelial cells... - Role of MLK3-mediated activation of p70 S6 kinase in Rac1 transformationJohn M Lambert
Lineberger Comprehensive Cancer Center, Department of Pharmacology and Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599 7295, USA
J Biol Chem 277:4770-7. 2002..These results suggest that MLK3 may be a negative regulator of the growth-promoting and transforming properties of Rac1... - Critical role of the pleckstrin homology domain in Dbs signaling and growth regulationErnesto J Fuentes
Department of Biochemistry and Biophysics, University of North Carolina, Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina 27599, USA
J Biol Chem 278:21188-96. 2003.... - Rnd proteins function as RhoA antagonists by activating p190 RhoGAPKrister Wennerberg
Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Curr Biol 13:1106-15. 2003..However, effector molecules of Rnd proteins with such properties have not been identified... - XPLN, a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoCWilliam T Arthur
Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
J Biol Chem 277:42964-72. 2002..In conclusion, here we describe a Rho family GEF that can discriminate between the closely related RhoA, RhoB, and RhoC, possibly giving insight to the divergent functions of these three proteins... - DLC-1 suppresses non-small cell lung cancer growth and invasion by RhoGAP-dependent and independent mechanismsKevin D Healy
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, NC 27599 7295, USA
Mol Carcinog 47:326-37. 2008..Combined, these studies provide information on the mechanism of DLC-1 function and regulation, and further support the role of DLC-1 tumor suppression in NSCLC... - Involvement of Ras activation in human breast cancer cell signaling, invasion, and anoikisLynn B Eckert
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295, USA
Cancer Res 64:4585-92. 2004.... - Aberrant receptor internalization and enhanced FRS2-dependent signaling contribute to the transforming activity of the fibroblast growth factor receptor 2 IIIb C3 isoformJiyoung Y Cha
Lineberger Comprehensive Cancer Center, Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599 7295, USA
J Biol Chem 284:6227-40. 2009..Our data support a dual mechanism where deletion of the 770YXXL773 motif promotes FGFR2 IIIb C3 transforming activity by causing aberrant receptor recycling and stability and persistent FRS2-dependent signaling... - Ras family signaling: therapeutic targetingAdrienne D Cox
University of North Carolina at Chapel Hill, North Carolina 27599, USA
Cancer Biol Ther 1:599-606. 2002..We review the current status of anti-Ras drug development, issues that have complicated their progression to the clinic, and possible future strategies for targeting Ras... - Raf-independent deregulation of p38 and JNK mitogen-activated protein kinases are critical for Ras transformationKevin Pruitt
University of North Carolina, Lineberger Comprehensive Cancer Center, Department of Pharmacology, Chapel Hill, North Carolina 27599, USA
J Biol Chem 277:31808-17. 2002..We conclude that a key action of Raf-independent effector pathways important for Ras transformation may involve inhibition of p38 and activation of JNK... - Ras-mediated intestinal epithelial cell transformation requires cyclooxygenase-2-induced prostaglandin E2 signalingGretchen A Repasky
Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Mol Carcinog 46:958-70. 2007..In summary, our studies define additional, multiple signaling mechanisms that promote COX-2 and PGE2 expression and show that COX-2-stimulated PGE2-EP receptor signaling is required for growth and survival transformation by Ras... - Distinct requirements for Ras oncogenesis in human versus mouse cellsNesrin M Hamad
Department of Pharmacology, Division of Neurology, Duke University Medical Center, Durham North Carolina 27710, USA
Genes Dev 16:2045-57. 2002..Thus, oncogenic Ras may transform murine and human cells by distinct mechanisms, and the RalGEF pathway--previously deemed to play a secondary role in Ras transformation--could represent a new target for anti-cancer therapy... - Tiam1 mediates Ras activation of Rac by a PI(3)K-independent mechanismJohn M Lambert
Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Nat Cell Biol 4:621-5. 2002..Furthermore, activated Ras and Tiam1 cooperate to cause synergistic formation of Rac-GTP in a PI(3)K-independent manner. Thus, Tiam1 can function as an effector that directly mediates Ras activation of Rac... - Genetic and pharmacologic dissection of Ras effector utilization in oncogenesisPaul M Campbell
Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Methods Enzymol 407:195-217. 2006.... - K-Ras promotes growth transformation and invasion of immortalized human pancreatic cells by Raf and phosphatidylinositol 3-kinase signalingPaul M Campbell
Lineberger Comprehensive Cancer Center and Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Cancer Res 67:2098-106. 2007..In summary, our studies established, characterized, and validated E6/E7/st cells for the study of Ras-induced oncogenesis... - Specificity and mechanism of action of EHT 1864, a novel small molecule inhibitor of Rac family small GTPasesAdam Shutes
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA
J Biol Chem 282:35666-78. 2007..Taken together, our results suggest that EHT 1864 selectively inhibits Rac downstream signaling and transformation by a novel mechanism involving guanine nucleotide displacement... - ROCK-generated contractility regulates breast epithelial cell differentiation in response to the physical properties of a three-dimensional collagen matrixMichele A Wozniak
Department of Pharmacology, University of Wisconsin, Madison, WI 53706, USA
J Cell Biol 163:583-95. 2003.... - Multiple sequence elements facilitate Chp Rho GTPase subcellular location, membrane association, and transforming activityEmily J Chenette
Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA
Mol Biol Cell 17:3108-21. 2006..In summary, the unique carboxy-terminal sequence elements that promote Chp subcellular location and function expand the complexity of mechanisms by which the cellular functions of Rho GTPases are regulated... - RhoA biological activity is dependent on prenylation but independent of specific isoprenoid modificationPatricia A Solski
University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, Departments of Pharmacology, Chapel Hill, North Carolina 27599, USA
Cell Growth Differ 13:363-73. 2002.... - Critical and distinct roles of amino- and carboxyl-terminal sequences in regulation of the biological activity of the Chp atypical Rho GTPaseEmily J Chenette
Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina 27599 7295, USA
J Biol Chem 280:13784-92. 2005..In summary, Chp is implicated in cell transformation, and the unique amino and carboxyl termini of Chp represent atypical mechanisms of regulation of Rho GTPase function... - Role of the pleckstrin homology domain in intersectin-L Dbl homology domain activation of Cdc42 and signalingWendy M Pruitt
Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA
Biochim Biophys Acta 1640:61-8. 2003..PH domains can interact with phosphoinositide substrates and products of phosphatidylinositol 3-kinase (PI3K). However, PI3K activation did not modulate ITSN-L DH domain function in vivo... - Rho Family GTPase modification and dependence on CAAX motif-signaled posttranslational modificationPatrick J Roberts
Lineberger Comprehensive Cancer Center, Division of Pharmacotherapy and Experimental Therapeutics, Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA
J Biol Chem 283:25150-63. 2008..We conclude that a majority of Rho GTPases are targets for pharmacologic inhibitors of farnesyltransferase, Rce1, and Icmt... - The dark side of Ras: regulation of apoptosisAdrienne D Cox
Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Oncogene 22:8999-9006. 2003.... - Involvement of phosphatidylinositol 3-kinase, but not RalGDS, in TC21/R-Ras2-mediated transformationGretchen A Murphy
Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599 7295, USA
J Biol Chem 277:9966-75. 2002..Finally, unlike Ras, TC21 did not activate the Rac small GTPase, indicating that Ras may not activate Rac by PI3K. Taken together, these results suggest that PI3K, but not RalGDS, is an important mediator of cell proliferation by TC21... - Effects of structure of Rho GTPase-activating protein DLC-1 on cell morphology and migrationTai Young Kim
Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
J Biol Chem 283:32762-70. 2008..Conversely, the expression of the amino-terminal domain of DLC-1 acts as a dominant negative and profoundly inhibits cell migration by displacing endogenous DLC-1 from focal adhesions... - TLN-4601 suppresses growth and induces apoptosis of pancreatic carcinoma cells through inhibition of Ras-ERK MAPK signalingPaul M Campbell
Lineberger Comprehensive Cancer Center and Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill NC 27599 7295, USA
J Mol Signal 5:18. 2010..Furthermore, RAS isoforms are the most frequently mutated oncogenes, occurring in approximately 30% of all human cancers, and KRAS is the most commonly mutated RAS gene, with a greater than 90% incidence of mutation in pancreatic cancer... - Use of retrovirus expression of interfering RNA to determine the contribution of activated K-Ras and ras effector expression to human tumor cell growthAntonio T Baines
Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Methods Enzymol 407:556-74. 2006..Finally, we also compare the use of constitutive and inducible shRNA expression vectors for analyses of mutant Ras function... - Farnesyltransferase inhibitors: promises and realitiesAdrienne D Cox
Department of Radiation Oncology CB 7512, 1050 Gravely Building, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7512, USA
Curr Opin Pharmacol 2:388-93. 2002..It is possible that the critical target downstream of farnesyltransferase responsible for these effects is not either Ras or RhoB, the two most cited possibilities - but the hunt is on... - Targeting signal transduction in pancreatic cancer treatmentJen Jen Yeh
University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, Division of Surgical Oncology, Chapel Hill, NC 27599, USA
Expert Opin Ther Targets 11:673-94. 2007..This review focuses on the validation of specific signaling networks and the present status of inhibitors of these pathways as therapeutic approaches for pancreatic cancer treatment... - Leukemia-associated Rho guanine nucleotide exchange factor promotes G alpha q-coupled activation of RhoAMichelle A Booden
Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 27599, USA
Mol Cell Biol 22:4053-61. 2002..Our findings suggest that the RhoA exchange factor LARG, unlike the related p115 RhoGEF and PDZ-RhoGEF proteins, can serve as an effector for Gq-coupled receptors, mediating their functional linkage to RhoA-dependent signaling pathways... - Critical but distinct roles for the pleckstrin homology and cysteine-rich domains as positive modulators of Vav2 signaling and transformationMichelle A Booden
Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
Mol Cell Biol 22:2487-97. 2002..In conclusion, the PH domain and CRD are mechanistically distinct, positive modulators of Vav2 DH domain function in vivo... - Opposing roles of the extracellular signal-regulated kinase and p38 mitogen-activated protein kinase cascades in Ras-mediated downregulation of tropomyosinJaniel M Shields
Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 27599, USA
Mol Cell Biol 22:2304-17. 2002..Finally, treatment with azadeoxycytidine restored tropomyosin expression in Ras-transformed RIE-1, HT1080, and DLD-1 cells, suggesting a role for DNA methylation in downregulating tropomyosin expression... - RasGRP4 is a novel Ras activator isolated from acute myeloid leukemiaGary W Reuther
Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7295, USA
J Biol Chem 277:30508-14. 2002..We conclude that RasGRP4 is a member of the RasGRP family of Ras guanine nucleotide exchange factors that may play a role in myeloid cell signaling growth regulation pathways that are responsive to diacylglycerol levels... 
Personalized medicine in non-small-cell lung cancer: is KRAS a useful marker in selecting patients for epidermal growth factor receptor-targeted therapy?Patrick J Roberts
Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599 7295, USA
J Clin Oncol 28:4769-77. 2010....- A six-gene signature predicts survival of patients with localized pancreatic ductal adenocarcinomaJeran K Stratford
Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
PLoS Med 7:e1000307. 2010.... - The raf inhibitor paradox: unexpected consequences of targeted drugsAdrienne D Cox
Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
Cancer Cell 17:221-3. 2010..This occurs only in "primed" cells bearing activated RAS and WT RAF, explaining the selective efficacy of RAF inhibitors for RAF mutant cells... - Atypical mechanism of regulation of the Wrch-1 Rho family small GTPaseAdam Shutes
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
Curr Biol 14:2052-6. 2004..We propose that Grb2 overcomes N-terminal negative regulation to promote Wrch-1 effector interaction. Thus, Wrch-1 exhibits an atypical model of regulation not seen in other Rho family GTPases... - KRAS/BRAF mutation status and ERK1/2 activation as biomarkers for MEK1/2 inhibitor therapy in colorectal cancerJen Jen Yeh
Department of Surgery, University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, 450 West Drive, CB 7295, Chapel Hill, NC 27599 7295, USA
Mol Cancer Ther 8:834-43. 2009..Our results suggest that although MEK inhibitors show promise in colorectal cancer, KRAS/BRAF mutation status, but not ERK activation as previously thought, may be useful biomarkers for MEK inhibitor sensitivity... - Auto-inhibition of the Dbl family protein Tim by an N-terminal helical motifMarielle E Yohe
Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599 7295, USA
J Biol Chem 282:13813-23. 2007..Furthermore, substitutions within the most highly conserved surface of the DH domain designed to disrupt interactions with the auto-inhibitory helix also activate the exchange process... - Molecular basis for Rho GTPase signaling specificityAntoine E Karnoub
Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA
Breast Cancer Res Treat 84:61-71. 2004..In this review, we highlight issues relating to the structural basis by which Dbl family GEFs facilitate signaling convergence and Rho GTPase activation, and how Rho GTPases promote signal dissemination through downstream effectors... - Oncogenic Ras and its role in tumor cell invasion and metastasisPaul M Campbell
Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, CB 7295, Chapel Hill, NC 27599 7295, USA
Semin Cancer Biol 14:105-14. 2004..In this review, we discuss the current evidence for mutant Ras proteins as significant players in these aspects of cancer progression... - Rho-family GTPases: it's not only Rac and Rho (and I like it)Krister Wennerberg
Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7295, USA
J Cell Sci 117:1301-12. 2004..Newer members of the family possess additional sequence elements beyond the GTPase domain, which suggests they exhibit yet other mechanisms of regulation... - Loss of transgelin in breast and colon tumors and in RIE-1 cells by Ras deregulation of gene expression through Raf-independent pathwaysJaniel M Shields
Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599 7295, USA
J Biol Chem 277:9790-9. 2002..We conclude that loss of transgelin gene expression may be an important early event in tumor progression and a diagnostic marker for breast and colon cancer development... - Rac1b, a tumor associated, constitutively active Rac1 splice variant, promotes cellular transformationAnurag Singh
Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Oncogene 23:9369-80. 2004..However, Rac1b did promote activation of the AKT serine/threonine kinase. Therefore, we suggest that Rac1b selectively activates a subset of Rac1 downstream signaling pathways to facilitate cellular transformation... - GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factorsKent L Rossman
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
Nat Rev Mol Cell Biol 6:167-80. 2005..The failure to do so can have significant consequences and is reflected in the aberrant function of Dbl-family GEFs in some human diseases... - RhoG signals in parallel with Rac1 and Cdc42Krister Wennerberg
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599 7295, USA
J Biol Chem 277:47810-7. 2002..Together, these data argue that RhoG function is mediated by signals independent of Rac1 and Cdc42 activation and instead by direct utilization of a subset of common effectors... - Biochemical analyses of the Wrch atypical Rho family GTPasesAdam Shutes
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, USA
Methods Enzymol 406:11-26. 2006..In this chapter, we summarize our experimental approaches used to characterize the biochemical properties of these atypical Rho GTPases... - Real-time in vitro measurement of GTP hydrolysisAdam Shutes
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, NC 27599 7295, USA
Methods 37:183-89. 2005..We also discuss the pros and cons, and implications of the technique in comparison to the radioactive and HPLC method of measuring the GTPase activity... - Signaling interplay in Ras superfamily functionNatalia Mitin
University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, NC 27599, USA
Curr Biol 15:R563-74. 2005..A key biochemical mechanism facilitating this crosstalk involves guanine nucleotide exchange factors (GEFs), which serve as regulators and effectors, as well as signaling integrators, of Ras signaling... - Enhanced cathepsin L expression is mediated by different Ras effector pathways in fibroblasts and epithelial cellsJohn Collette
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA
Int J Cancer 112:190-9. 2004..Thus, Ras utilizes different effectors to mediate transformation and to deregulate cathepsin L expression and secretion in fibroblast and epithelial cells... - Real-time in vitro measurement of intrinsic and Ras GAP-mediated GTP hydrolysisAdam Shutes
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Methods Enzymol 407:9-22. 2006..We have used the Ras family small GTPase R-Ras and the GAP-related domain from neurofibromin to demonstrate the application of these protocols... - Ligand-dependent dynamics and intramolecular signaling in a PDZ domainErnesto J Fuentes
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
J Mol Biol 335:1105-15. 2004.... - Requirement for C-terminal sequences in regulation of Ect2 guanine nucleotide exchange specificity and transformationPatricia A Solski
Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
J Biol Chem 279:25226-33. 2004..Taken together, these observations suggest that regions of Ect2 C-terminal to the DH domain alter the profile of Rho GTPases activated in vivo and consequently may contribute to the enhanced transforming activity of DeltaN-Ect2 DH/PH/C... - Identification and characterization of rain, a novel Ras-interacting protein with a unique subcellular localizationNatalia Y Mitin
Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907 2054, USA
J Biol Chem 279:22353-61. 2004..Taken together, these observations support a role for Rain as a novel protein that can serve as an effector of endomembrane-localized Ras... - Divergent roles for RalA and RalB in malignant growth of human pancreatic carcinoma cellsKian Huat Lim
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
Curr Biol 16:2385-94. 2006..In the present study, we determined whether RalA and RalB also had divergent roles in promoting the aberrant growth of pancreatic cancers, which are characterized by the highest occurrence of Ras mutations... - Overexpression of collagenase 1 (MMP-1) is mediated by the ERK pathway in invasive melanoma cells: role of BRAF mutation and fibroblast growth factor signalingJonathan T Huntington
Norris Cotton Cancer Center, Departments of Physiology, Medicine, and Biochemistry, Dartmouth Medical School, Lebanon NH 03756, USA
J Biol Chem 279:33168-76. 2004..Thus, constitutive activation of this MAPK pathway not only promotes the increased proliferation of melanoma cells but is also important for the acquisition of an invasive phenotype... - Activation of RalA is critical for Ras-induced tumorigenesis of human cellsKian Huat Lim
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
Cancer Cell 7:533-45. 2005..Activation of RalA signaling thus appears to be a critical step in Ras-induced transformation and tumorigenesis of human cells... - Cellular N-Ras promotes cell survival by downregulation of Jun N-terminal protein kinase and p38Janice C Wolfman
Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
Mol Cell Biol 22:1589-606. 2002.... - The Ras superfamily at a glanceKrister Wennerberg
Cytoskeleton Inc, 1830 S. Acoma Street, Denver, CO 80223, USA
J Cell Sci 118:843-6. 2005 - Geranylgeranyltransferase I inhibitors target RalB to inhibit anchorage-dependent growth and induce apoptosis and RalA to inhibit anchorage-independent growthSamuel C Falsetti
Drug Discovery Program, The H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
Mol Cell Biol 27:8003-14. 2007..We conclude that RalA and RalB are important, functionally distinct targets for GGTI-mediated tumor apoptosis and growth inhibition... - Role of MAP kinases in the 1,25-dihydroxyvitamin D3-induced transactivation of the rat cytochrome P450C24 (CYP24) promoter. Specific functions for ERK1/ERK2 and ERK5Prem P Dwivedi
Department of Molecular Biosciences Biochemistry, University of Adelaide, Adelaide, Australia 5005
J Biol Chem 277:29643-53. 2002..The ERK1/ERK2 and ERK5 modules provide a novel mechanism for linking the rapid signal transduction and slower transcription actions of 1,25D to induce CYP24 gene expression... - The G12 family of heterotrimeric G proteins promotes breast cancer invasion and metastasisPatrick Kelly
Department Pharmacology, Duke University Medical Center, Durham, NC 27710, USA
Proc Natl Acad Sci U S A 103:8173-8. 2006....
Research Grants
- Aberrant LARG and RhoA activation in human leukemiasChanning Der; Fiscal Year: 2005..Our studies will provide a comprehensive, structural, biochemical, and biological analysis of LARG function and assess a role for aberrant LARG activation of RhoA in AML development. ..
- Role of RGS proteins in Ras- and B-Raf--mediated transformationChanning J Der; Fiscal Year: 2010....
- BIOLOGICAL ACTIVITY OF RAS ONCOGENESChanning J Der; Fiscal Year: 2010..Therefore, we believe that our studies to better understand how this pathway, the RalGEF-Ral pathway, promotes Ras- driven cancer growth will lead to our identification of novel drugs for the effective treatment of pancreatic cancer. ..
- RAS SIGNAL TRANSDUCTION AND TRANSFORMATIONChanning Der; Fiscal Year: 2006....
- BIOLOGICAL ACTIVITY OF RAS ONCOGENESChanning Der; Fiscal Year: 2004..Our studies may refocus future efforts to target other Ras signaling pathways for the development of novel therapeutic agents for cancer treatment. ..
- RHO FAMILY PROTEINS AND MALIGNANT TRANSFORMATIONChanning Der; Fiscal Year: 2007..abstract_text> ..
- Mechanism and role of DLC-1 tumor suppressor loss in lung cancerChanning J Der; Fiscal Year: 2010..Hence, we believe that our elucidation of the mechanism by which DLC-1 loss may deregulate Rho GTPases and promote NSCLC growth may define novel directions for targeted therapies for lung cancer treatment. ..
- Role of RGS proteins in Ras- and B-Raf--mediated transformationChanning Der; Fiscal Year: 2009....
- BIOLOGICAL ACTIVITY OF RAS ONCOGENESChanning Der; Fiscal Year: 2009..abstract_text> ..
- CANCER CELL BIOLOGY TRAINING PROGRAMChanning Der; Fiscal Year: 2007....
- Role of RGS proteins in Ras- and B-Raf--mediated transformationChanning Der; Fiscal Year: 2007....
- BIOLOGICAL ACTIVITY OF RAS ONCOGENESChanning Der; Fiscal Year: 1999..g., the MEK/MAPK serine/threonine kinases) may represent novel targets for rational drug design. The studies that we have proposed will provide further insight into both possibilities. ..
- RHO FAMILY PROTEINS AND MALIGNANT TRANSFORMATIONChanning Der; Fiscal Year: 2002..Taken together, these studies will elucidate the mechanisms by which Rho and Dbl family proteins may promote malignant transformation. ..
- RAS SIGNAL TRANSDUCTION AND TRANSFORMATIONChanning Der; Fiscal Year: 2000....