Channing Der

Summary

Affiliation: University of North Carolina
Country: USA

Publications

  1. ncbi request reprint Stopping ras in its tracks
    Channing 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
  2. pmc Effects of structure of Rho GTPase-activating protein DLC-1 on cell morphology and migration
    Tai Young Kim
    Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 283:32762-70. 2008
  3. pmc Differential involvement of RalA and RalB in colorectal cancer
    Timothy D Martin
    Deparment of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    Small Gtpases 3:126-30. 2012
  4. pmc Differential requirement of CAAX-mediated posttranslational processing for Rheb localization and signaling
    A B Hanker
    Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7295, USA
    Oncogene 29:380-91. 2010
  5. pmc The RalB small GTPase mediates formation of invadopodia through a GTPase-activating protein-independent function of the RalBP1/RLIP76 effector
    Nicole 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
  6. pmc Genetic and functional characterization of putative Ras/Raf interaction inhibitors in C. elegans and mammalian cells
    Vanessa 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
  7. pmc Romidepsin inhibits Ras-dependent growth transformation of NIH 3T3 fibroblasts and RIE-1 epithelial cells independently of Ras signaling inhibition
    Ariella 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
  8. ncbi request reprint Vav transformation requires activation of multiple GTPases and regulation of gene expression
    Todd 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
  9. ncbi request reprint Structural basis for the selective activation of Rho GTPases by Dbl exchange factors
    Jason 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
  10. ncbi request reprint Transforming activity of the Rho family GTPase, Wrch-1, a Wnt-regulated Cdc42 homolog, is dependent on a novel carboxyl-terminal palmitoylation motif
    Anastacia C Berzat
    Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, 27599 7512, USA
    J Biol Chem 280:33055-65. 2005

Research Grants

  1. Aberrant LARG and RhoA activation in human leukemias
    Channing Der; Fiscal Year: 2005
  2. Role of RGS proteins in Ras- and B-Raf--mediated transformation
    Channing J Der; Fiscal Year: 2010
  3. BIOLOGICAL ACTIVITY OF RAS ONCOGENES
    Channing J Der; Fiscal Year: 2010
  4. RAS SIGNAL TRANSDUCTION AND TRANSFORMATION
    Channing Der; Fiscal Year: 2006
  5. BIOLOGICAL ACTIVITY OF RAS ONCOGENES
    Channing Der; Fiscal Year: 2006
  6. RHO FAMILY PROTEINS AND MALIGNANT TRANSFORMATION
    Channing Der; Fiscal Year: 2005
  7. RAS SIGNAL TRANSDUCTION AND TRANSFORMATION
    Channing Der; Fiscal Year: 2005
  8. BIOLOGICAL ACTIVITY OF RAS ONCOGENES
    Channing Der; Fiscal Year: 2005
  9. Aberrant LARG and RhoA activation in human leukemias
    Channing Der; Fiscal Year: 2004
  10. RHO FAMILY PROTEINS AND MALIGNANT TRANSFORMATION
    Channing Der; Fiscal Year: 2004

Detail Information

Publications75

  1. ncbi request reprint Stopping ras in its tracks
    Channing 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...
  2. pmc Effects of structure of Rho GTPase-activating protein DLC-1 on cell morphology and migration
    Tai 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...
  3. pmc Differential involvement of RalA and RalB in colorectal cancer
    Timothy D Martin
    Deparment of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    Small Gtpases 3:126-30. 2012
    ..Our results emphasize cancer cell type differences in Ral function and hence the need for distinct Ral targeted therapeutic approaches in the treatment of CRC vs. PDAC...
  4. pmc Differential requirement of CAAX-mediated posttranslational processing for Rheb localization and signaling
    A B Hanker
    Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7295, USA
    Oncogene 29:380-91. 2010
    ..We conclude that inhibitors of Icmt and Rce1 will not block Rheb function, but FTS could be a promising treatment for Rheb- and mTOR-dependent cancers...
  5. pmc The RalB small GTPase mediates formation of invadopodia through a GTPase-activating protein-independent function of the RalBP1/RLIP76 effector
    Nicole 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...
  6. pmc Genetic and functional characterization of putative Ras/Raf interaction inhibitors in C. elegans and mammalian cells
    Vanessa 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
    ....
  7. pmc Romidepsin inhibits Ras-dependent growth transformation of NIH 3T3 fibroblasts and RIE-1 epithelial cells independently of Ras signaling inhibition
    Ariella 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...
  8. ncbi request reprint Vav transformation requires activation of multiple GTPases and regulation of gene expression
    Todd 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
    ....
  9. ncbi request reprint Structural basis for the selective activation of Rho GTPases by Dbl exchange factors
    Jason 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
    ....
  10. ncbi request reprint Transforming activity of the Rho family GTPase, Wrch-1, a Wnt-regulated Cdc42 homolog, is dependent on a novel carboxyl-terminal palmitoylation motif
    Anastacia 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...
  11. ncbi request reprint p68RacGAP is a novel GTPase-activating protein that interacts with vascular endothelial zinc finger-1 and modulates endothelial cell capillary formation
    Julius 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
    ....
  12. ncbi request reprint Essential role of Raf in Ras transformation and deregulation of matrix metalloproteinase expression in ovarian epithelial cells
    Aylin 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...
  13. ncbi request reprint Critical role of the pleckstrin homology and cysteine-rich domains in Vav signaling and transforming activity
    Todd 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...
  14. ncbi request reprint 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 cells
    Kevin Pruitt
    Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, 27599 7295, USA
    J Biol Chem 280:23363-70. 2005
    ....
  15. ncbi request reprint Role of MLK3-mediated activation of p70 S6 kinase in Rac1 transformation
    John 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...
  16. ncbi request reprint Critical role of the pleckstrin homology domain in Dbs signaling and growth regulation
    Ernesto 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
    ....
  17. ncbi request reprint XPLN, a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoC
    William 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...
  18. pmc DLC-1 suppresses non-small cell lung cancer growth and invasion by RhoGAP-dependent and independent mechanisms
    Kevin 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...
  19. ncbi request reprint Rnd proteins function as RhoA antagonists by activating p190 RhoGAP
    Krister 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...
  20. ncbi request reprint Involvement of Ras activation in human breast cancer cell signaling, invasion, and anoikis
    Lynn 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
    ....
  21. pmc Aberrant receptor internalization and enhanced FRS2-dependent signaling contribute to the transforming activity of the fibroblast growth factor receptor 2 IIIb C3 isoform
    Jiyoung 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...
  22. ncbi request reprint Ras-mediated intestinal epithelial cell transformation requires cyclooxygenase-2-induced prostaglandin E2 signaling
    Gretchen 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...
  23. ncbi request reprint Ras family signaling: therapeutic targeting
    Adrienne 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...
  24. ncbi request reprint Raf-independent deregulation of p38 and JNK mitogen-activated protein kinases are critical for Ras transformation
    Kevin 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...
  25. pmc Distinct requirements for Ras oncogenesis in human versus mouse cells
    Nesrin 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...
  26. ncbi request reprint Tiam1 mediates Ras activation of Rac by a PI(3)K-independent mechanism
    John 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...
  27. ncbi request reprint Genetic and pharmacologic dissection of Ras effector utilization in oncogenesis
    Paul 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
    ....
  28. ncbi request reprint K-Ras promotes growth transformation and invasion of immortalized human pancreatic cells by Raf and phosphatidylinositol 3-kinase signaling
    Paul 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...
  29. ncbi request reprint Specificity and mechanism of action of EHT 1864, a novel small molecule inhibitor of Rac family small GTPases
    Adam 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...
  30. ncbi request reprint Critical and distinct roles of amino- and carboxyl-terminal sequences in regulation of the biological activity of the Chp atypical Rho GTPase
    Emily 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...
  31. pmc Multiple sequence elements facilitate Chp Rho GTPase subcellular location, membrane association, and transforming activity
    Emily 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...
  32. ncbi request reprint RhoA biological activity is dependent on prenylation but independent of specific isoprenoid modification
    Patricia 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
    ....
  33. ncbi request reprint The dark side of Ras: regulation of apoptosis
    Adrienne 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
    ....
  34. pmc ROCK-generated contractility regulates breast epithelial cell differentiation in response to the physical properties of a three-dimensional collagen matrix
    Michele A Wozniak
    Department of Pharmacology, University of Wisconsin, Madison, WI 53706, USA
    J Cell Biol 163:583-95. 2003
    ....
  35. ncbi request reprint Role of the pleckstrin homology domain in intersectin-L Dbl homology domain activation of Cdc42 and signaling
    Wendy 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...
  36. pmc Rho Family GTPase modification and dependence on CAAX motif-signaled posttranslational modification
    Patrick 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...
  37. pmc TLN-4601 suppresses growth and induces apoptosis of pancreatic carcinoma cells through inhibition of Ras-ERK MAPK signaling
    Paul 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...
  38. ncbi request reprint Biochemical analyses of the Wrch atypical Rho family GTPases
    Adam 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...
  39. ncbi request reprint Targeting signal transduction in pancreatic cancer treatment
    Jen 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...
  40. pmc KRAS/BRAF mutation status and ERK1/2 activation as biomarkers for MEK1/2 inhibitor therapy in colorectal cancer
    Jen 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...
  41. doi request reprint 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
    ....
  42. ncbi request reprint Auto-inhibition of the Dbl family protein Tim by an N-terminal helical motif
    Marielle 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...
  43. ncbi request reprint The raf inhibitor paradox: unexpected consequences of targeted drugs
    Adrienne 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...
  44. pmc A six-gene signature predicts survival of patients with localized pancreatic ductal adenocarcinoma
    Jeran 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
    ....
  45. ncbi request reprint Use of retrovirus expression of interfering RNA to determine the contribution of activated K-Ras and ras effector expression to human tumor cell growth
    Antonio 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...
  46. ncbi request reprint Real-time in vitro measurement of GTP hydrolysis
    Adam 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...
  47. ncbi request reprint Signaling interplay in Ras superfamily function
    Natalia 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...
  48. ncbi request reprint 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...
  49. ncbi request reprint Oncogenic Ras and its role in tumor cell invasion and metastasis
    Paul 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...
  50. ncbi request reprint Molecular basis for Rho GTPase signaling specificity
    Antoine 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...
  51. ncbi request reprint RhoG signals in parallel with Rac1 and Cdc42
    Krister 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...
  52. ncbi request reprint Farnesyltransferase inhibitors: promises and realities
    Adrienne 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...
  53. pmc Leukemia-associated Rho guanine nucleotide exchange factor promotes G alpha q-coupled activation of RhoA
    Michelle 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...
  54. pmc Critical but distinct roles for the pleckstrin homology and cysteine-rich domains as positive modulators of Vav2 signaling and transformation
    Michelle 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...
  55. pmc Opposing roles of the extracellular signal-regulated kinase and p38 mitogen-activated protein kinase cascades in Ras-mediated downregulation of tropomyosin
    Janiel 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...
  56. ncbi request reprint RasGRP4 is a novel Ras activator isolated from acute myeloid leukemia
    Gary 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...
  57. ncbi request reprint Involvement of phosphatidylinositol 3-kinase, but not RalGDS, in TC21/R-Ras2-mediated transformation
    Gretchen 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...
  58. ncbi request reprint Loss of transgelin in breast and colon tumors and in RIE-1 cells by Ras deregulation of gene expression through Raf-independent pathways
    Janiel 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...
  59. ncbi request reprint GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors
    Kent 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...
  60. ncbi request reprint Atypical mechanism of regulation of the Wrch-1 Rho family small GTPase
    Adam 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...
  61. ncbi request reprint Rac1b, a tumor associated, constitutively active Rac1 splice variant, promotes cellular transformation
    Anurag 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...
  62. ncbi request reprint Requirement for C-terminal sequences in regulation of Ect2 guanine nucleotide exchange specificity and transformation
    Patricia 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...
  63. ncbi request reprint Ligand-dependent dynamics and intramolecular signaling in a PDZ domain
    Ernesto 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
    ....
  64. ncbi request reprint Enhanced cathepsin L expression is mediated by different Ras effector pathways in fibroblasts and epithelial cells
    John 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...
  65. ncbi request reprint Real-time in vitro measurement of intrinsic and Ras GAP-mediated GTP hydrolysis
    Adam 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...
  66. pmc SGEF, a RhoG guanine nucleotide exchange factor that stimulates macropinocytosis
    Shawn M Ellerbroek
    Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Mol Biol Cell 15:3309-19. 2004
    ..Together, this work establishes SGEF as a RhoG exchange factor and provides evidence that both SGEF and RhoG regulate membrane dynamics in promotion of macropinocytosis...
  67. pmc Cellular N-Ras promotes cell survival by downregulation of Jun N-terminal protein kinase and p38
    Janice C Wolfman
    Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Mol Cell Biol 22:1589-606. 2002
    ....
  68. ncbi request reprint The Ras superfamily at a glance
    Krister Wennerberg
    Cytoskeleton Inc, 1830 S Acoma Street, Denver, CO 80223, USA
    J Cell Sci 118:843-6. 2005
  69. pmc The G12 family of heterotrimeric G proteins promotes breast cancer invasion and metastasis
    Patrick Kelly
    Department Pharmacology, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 103:8173-8. 2006
    ....
  70. ncbi request reprint Activation of RalA is critical for Ras-induced tumorigenesis of human cells
    Kian 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...
  71. ncbi request reprint Divergent roles for RalA and RalB in malignant growth of human pancreatic carcinoma cells
    Kian 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...
  72. ncbi request reprint 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 ERK5
    Prem 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...
  73. ncbi request reprint Overexpression of collagenase 1 (MMP-1) is mediated by the ERK pathway in invasive melanoma cells: role of BRAF mutation and fibroblast growth factor signaling
    Jonathan 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...
  74. pmc Geranylgeranyltransferase I inhibitors target RalB to inhibit anchorage-dependent growth and induce apoptosis and RalA to inhibit anchorage-independent growth
    Samuel 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...
  75. ncbi request reprint Identification and characterization of rain, a novel Ras-interacting protein with a unique subcellular localization
    Natalia 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...

Research Grants55

  1. Aberrant LARG and RhoA activation in human leukemias
    Channing 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. ..
  2. Role of RGS proteins in Ras- and B-Raf--mediated transformation
    Channing J Der; Fiscal Year: 2010
    ....
  3. BIOLOGICAL ACTIVITY OF RAS ONCOGENES
    Channing 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. ..
  4. RAS SIGNAL TRANSDUCTION AND TRANSFORMATION
    Channing Der; Fiscal Year: 2006
    ....
  5. BIOLOGICAL ACTIVITY OF RAS ONCOGENES
    Channing Der; Fiscal Year: 2006
    ..abstract_text> ..
  6. RHO FAMILY PROTEINS AND MALIGNANT TRANSFORMATION
    Channing Der; Fiscal Year: 2005
    ..abstract_text> ..
  7. RAS SIGNAL TRANSDUCTION AND TRANSFORMATION
    Channing Der; Fiscal Year: 2005
    ....
  8. BIOLOGICAL ACTIVITY OF RAS ONCOGENES
    Channing Der; Fiscal Year: 2005
    ..abstract_text> ..
  9. Aberrant LARG and RhoA activation in human leukemias
    Channing Der; Fiscal Year: 2004
    ..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. ..
  10. RHO FAMILY PROTEINS AND MALIGNANT TRANSFORMATION
    Channing Der; Fiscal Year: 2004
    ..abstract_text> ..
  11. RAS SIGNAL TRANSDUCTION AND TRANSFORMATION
    Channing Der; Fiscal Year: 2004
    ....
  12. BIOLOGICAL ACTIVITY OF RAS ONCOGENES
    Channing 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. ..
  13. RHO FAMILY PROTEINS AND MALIGNANT TRANSFORMATION
    Channing Der; Fiscal Year: 2003
    ..abstract_text> ..
  14. RHO FAMILY PROTEINS AND MALIGNANT TRANSFORMATION
    Channing Der; Fiscal Year: 2006
    ..abstract_text> ..
  15. BIOLOGICAL ACTIVITY OF RAS ONCOGENES
    Channing Der; Fiscal Year: 2007
    ..abstract_text> ..
  16. RHO FAMILY PROTEINS AND MALIGNANT TRANSFORMATION
    Channing Der; Fiscal Year: 2007
    ..abstract_text> ..
  17. Mechanism and role of DLC-1 tumor suppressor loss in lung cancer
    Channing 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. ..
  18. Mechanism and role of DLC-1 tumor suppressor loss in lung cancer
    Channing Der; Fiscal Year: 2009
    ..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. ..
  19. Role of RGS proteins in Ras- and B-Raf--mediated transformation
    Channing Der; Fiscal Year: 2009
    ....
  20. BIOLOGICAL ACTIVITY OF RAS ONCOGENES
    Channing Der; Fiscal Year: 2009
    ..abstract_text> ..
  21. Mechanism and role of DLC-1 tumor suppressor loss in lung cancer
    Channing Der; Fiscal Year: 2008
    ..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. ..
  22. CANCER CELL BIOLOGY TRAINING PROGRAM
    Channing Der; Fiscal Year: 2008
    ....
  23. Role of RGS proteins in Ras- and B-Raf--mediated transformation
    Channing Der; Fiscal Year: 2008
    ....
  24. BIOLOGICAL ACTIVITY OF RAS ONCOGENES
    Channing Der; Fiscal Year: 2008
    ..abstract_text> ..
  25. CANCER CELL BIOLOGY TRAINING PROGRAM
    Channing Der; Fiscal Year: 2007
    ....
  26. Role of RGS proteins in Ras- and B-Raf--mediated transformation
    Channing Der; Fiscal Year: 2007
    ....
  27. BIOLOGICAL ACTIVITY OF RAS ONCOGENES
    Channing Der; Fiscal Year: 2003
    ..Our studies may refocus future efforts to target other Ras signaling pathways for the development of novel therapeutic agents for cancer treatment. ..
  28. RAS SIGNAL TRANSDUCTION AND TRANSFORMATION
    Channing Der; Fiscal Year: 2003
    ....
  29. Aberrant LARG and RhoA activation in human leukemias
    Channing Der; Fiscal Year: 2003
    ..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. ..
  30. BIOLOGICAL ACTIVITY OF RAS ONCOGENES
    Channing 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. ..
  31. RHO FAMILY PROTEINS AND MALIGNANT TRANSFORMATION
    Channing Der; Fiscal Year: 1999
    ..Taken together, these studies will elucidate the mechanisms by which Rho and Dbl family proteins may promote malignant transformation. ..
  32. Aberrant LARG and RhoA activation in human leukemias
    Channing Der; Fiscal Year: 2002
    ..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. ..
  33. RHO FAMILY PROTEINS AND MALIGNANT TRANSFORMATION
    Channing Der; Fiscal Year: 2002
    ..Taken together, these studies will elucidate the mechanisms by which Rho and Dbl family proteins may promote malignant transformation. ..
  34. BIOLOGICAL ACTIVITY OF RAS ONCOGENES
    Channing Der; Fiscal Year: 2002
    ..Our studies may refocus future efforts to target other Ras signaling pathways for the development of novel therapeutic agents for cancer treatment. ..
  35. RAS SIGNAL TRANSDUCTION AND TRANSFORMATION
    Channing Der; Fiscal Year: 2002
    ....
  36. Aberrant LARG and RhoA activation in human leukemias
    Channing Der; Fiscal Year: 2001
    ..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. ..
  37. RHO FAMILY PROTEINS AND MALIGNANT TRANSFORMATION
    Channing Der; Fiscal Year: 2001
    ..Taken together, these studies will elucidate the mechanisms by which Rho and Dbl family proteins may promote malignant transformation. ..
  38. BIOLOGICAL ACTIVITY OF RAS ONCOGENES
    Channing Der; Fiscal Year: 2001
    ..Our studies may refocus future efforts to target other Ras signaling pathways for the development of novel therapeutic agents for cancer treatment. ..
  39. RAS SIGNAL TRANSDUCTION AND TRANSFORMATION
    Channing Der; Fiscal Year: 2000
    ....
  40. RHO FAMILY PROTEINS AND MALIGNANT TRANSFORMATION
    Channing Der; Fiscal Year: 2000
    ..Taken together, these studies will elucidate the mechanisms by which Rho and Dbl family proteins may promote malignant transformation. ..
  41. BIOLOGICAL ACTIVITY OF RAS ONCOGENES
    Channing Der; Fiscal Year: 2000
    ..Our studies may refocus future efforts to target other Ras signaling pathways for the development of novel therapeutic agents for cancer treatment. ..
  42. RAS SIGNAL TRANSDUCTION AND TRANSFORMATION
    Channing Der; Fiscal Year: 1999
    ....