Lee Graves

Summary

Affiliation: University of North Carolina
Country: USA

Publications

  1. pmc Application of multiplexed kinase inhibitor beads to study kinome adaptations in drug-resistant leukemia
    Matthew J Cooper
    Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America
    PLoS ONE 8:e66755. 2013
  2. pmc The dynamic nature of the kinome
    Lee M Graves
    The Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Biochem J 450:1-8. 2013
  3. pmc Generation of tumor-initiating cells by exogenous delivery of OCT4 transcription factor
    Adriana S Beltran
    Department of Pharmacology, The University of North Carolina at Chapel Hill, 120 Mason Farm Road, Chapel Hill, NC 27599, USA
    Breast Cancer Res 13:R94. 2011
  4. ncbi request reprint "Going KiNativ": probing the Native Kinome
    Lee M Graves
    Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7365, USA
    Chem Biol 18:683-4. 2011
  5. ncbi request reprint An intracellular calcium signal activates p70 but not p90 ribosomal S6 kinase in liver epithelial cells
    L M Graves
    Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599 7295, USA
    J Biol Chem 272:1920-8. 1997
  6. ncbi request reprint Regulation of carbamoyl phosphate synthetase by MAP kinase
    L M Graves
    Department of Pharmacology, Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 27599 7365, USA
    Nature 403:328-32. 2000
  7. ncbi request reprint Dependence of peroxisome proliferator-activated receptor ligand-induced mitogen-activated protein kinase signaling on epidermal growth factor receptor transactivation
    Olivia S Gardner
    Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    J Biol Chem 278:46261-9. 2003
  8. ncbi request reprint Role of Ras in metal-induced EGF receptor signaling and NF-kappaB activation in human airway epithelial cells
    Weidong Wu
    Center for Environmental Medicine and Lung Biology, University of North Carolina, Chapel Hill 27599, USA
    Am J Physiol Lung Cell Mol Physiol 282:L1040-8. 2002
  9. ncbi request reprint Inactivation of the antiapoptotic phosphatidylinositol 3-kinase-Akt pathway by the combined treatment of taxol and mitogen-activated protein kinase kinase inhibition
    Jeffrey P Mackeigan
    Lineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Clin Cancer Res 8:2091-9. 2002
  10. ncbi request reprint Induction of apoptosis in IL-3-dependent hematopoietic cell lines by guanine nucleotide depletion
    Jing Jin Gu
    Lineberger Comprehensive Cancer Center, Department of Pharmacology, University of North Carolina at Chapel Hill, 27599, USA
    Blood 101:4958-65. 2003

Collaborators

Detail Information

Publications38

  1. pmc Application of multiplexed kinase inhibitor beads to study kinome adaptations in drug-resistant leukemia
    Matthew J Cooper
    Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America
    PLoS ONE 8:e66755. 2013
    ..These results demonstrate the utility of MIB/MS as a tool to identify dysregulated kinases and to interrogate kinome dynamics as cells respond to targeted kinase inhibition. ..
  2. pmc The dynamic nature of the kinome
    Lee M Graves
    The Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Biochem J 450:1-8. 2013
    ..The development of technologies to study the kinome, as well as examples of kinome resilience and reprogramming, will be discussed in the present review...
  3. pmc Generation of tumor-initiating cells by exogenous delivery of OCT4 transcription factor
    Adriana S Beltran
    Department of Pharmacology, The University of North Carolina at Chapel Hill, 120 Mason Farm Road, Chapel Hill, NC 27599, USA
    Breast Cancer Res 13:R94. 2011
    ..Herein, we describe the generation of TIC-like cell lines by ectopic expression of the OCT4 transcription factor (TF) in primary breast cell preparations...
  4. ncbi request reprint "Going KiNativ": probing the Native Kinome
    Lee M Graves
    Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7365, USA
    Chem Biol 18:683-4. 2011
    ....
  5. ncbi request reprint An intracellular calcium signal activates p70 but not p90 ribosomal S6 kinase in liver epithelial cells
    L M Graves
    Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599 7295, USA
    J Biol Chem 272:1920-8. 1997
    ..In summary, these results demonstrate that intracellular calcium selectively activates p70(S6K) in GN4 cells, consistent with increased CADTK/PYK-2 signaling in these cells...
  6. ncbi request reprint Regulation of carbamoyl phosphate synthetase by MAP kinase
    L M Graves
    Department of Pharmacology, Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 27599 7365, USA
    Nature 403:328-32. 2000
    ..Hence these studies may indicate a direct link between activation of the MAP kinase cascade and de novo biosynthesis of pyrimidine nucleotides...
  7. ncbi request reprint Dependence of peroxisome proliferator-activated receptor ligand-induced mitogen-activated protein kinase signaling on epidermal growth factor receptor transactivation
    Olivia S Gardner
    Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    J Biol Chem 278:46261-9. 2003
    ..In summary, PPARalpha and gamma ligands activate two distinct signaling cascades in GN4 cells leading to MAPK activation...
  8. ncbi request reprint Role of Ras in metal-induced EGF receptor signaling and NF-kappaB activation in human airway epithelial cells
    Weidong Wu
    Center for Environmental Medicine and Lung Biology, University of North Carolina, Chapel Hill 27599, USA
    Am J Physiol Lung Cell Mol Physiol 282:L1040-8. 2002
    ..Together, these data suggest that, in V-treated BEAS-2B cells, Ras-dependent signaling is essential, but not sufficient, for activation of NF-kappaB...
  9. ncbi request reprint Inactivation of the antiapoptotic phosphatidylinositol 3-kinase-Akt pathway by the combined treatment of taxol and mitogen-activated protein kinase kinase inhibition
    Jeffrey P Mackeigan
    Lineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Clin Cancer Res 8:2091-9. 2002
    ..Overall, these findings render the combined use of paclitaxel with MEK inhibitors, or paclitaxel with PI3K inhibitors, as a promising new strategy for cancer chemotherapy...
  10. ncbi request reprint Induction of apoptosis in IL-3-dependent hematopoietic cell lines by guanine nucleotide depletion
    Jing Jin Gu
    Lineberger Comprehensive Cancer Center, Department of Pharmacology, University of North Carolina at Chapel Hill, 27599, USA
    Blood 101:4958-65. 2003
    ..These results indicate that IMPDH inhibitors may be effective in modulating signal transduction pathways in hematopoietic cells, suggesting their usefulness in chemotherapeutic regimens for hematologic malignancies...
  11. ncbi request reprint Src-dependent phosphorylation of the epidermal growth factor receptor on tyrosine 845 is required for zinc-induced Ras activation
    Weidong Wu
    Center for Environmental Medicine and Lung Biology, The Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 277:24252-7. 2002
    ..These data demonstrate that Src-dependent phosphorylation of the EGFR at Tyr-845 is required for EGFR transactivation and Zn2+-induced Ras activation...
  12. ncbi request reprint MAPK kinase kinases (MKKKs) as a target class for small-molecule inhibition to modulate signaling networks and gene expression
    Gary L Johnson
    Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, NC 27599 7365, USA
    Curr Opin Chem Biol 9:325-31. 2005
    ....
  13. ncbi request reprint p38 and EGF receptor kinase-mediated activation of the phosphatidylinositol 3-kinase/Akt pathway is required for Zn2+-induced cyclooxygenase-2 expression
    Weidong Wu
    Division of Immunology and Infectious Disease, Department of Pediatrics, University of North Carolina, Chapel Hill, NC 27599, USA
    Am J Physiol Lung Cell Mol Physiol 289:L883-9. 2005
    ..These data suggest that p38 and EGFR kinase-mediated Akt activation is required for Zn2+-induced COX-2 expression and that the PI3K/Akt signaling pathway plays a central role in this event...
  14. ncbi request reprint Diesel exhaust particulate-induced activation of Stat3 requires activities of EGFR and Src in airway epithelial cells
    Dongsun Cao
    Center for Environmental Medicine, Asthma and Lung Biology, University of North Carolina, Chapel Hill, NC 27599, USA
    Am J Physiol Lung Cell Mol Physiol 292:L422-9. 2007
    ..These findings demonstrate that DEP inhalation can activate proinflammatory Stat3 signaling in vitro...
  15. ncbi request reprint Peroxisome proliferator-activated receptor gamma-independent activation of p38 MAPK by thiazolidinediones involves calcium/calmodulin-dependent protein kinase II and protein kinase R: correlation with endoplasmic reticulum stress
    Olivia S Gardner
    Curriculum in Toxicology, University of North Carolina at Chapel Hill, North Carolina, 27599, USA
    J Biol Chem 280:10109-18. 2005
    ..Furthermore, using structural derivatives of TZDs that lack PPARgamma ligand-binding activity as well as a PPARgamma antagonist, we show that activation of these kinase signaling pathways is PPARgamma-independent...
  16. ncbi request reprint Phosphorylation of insulin receptor substrate-1 serine 307 correlates with JNK activity in atrophic skeletal muscle
    Thomas L Hilder
    Department of Pharmacology, University of North Carolina, Chapel Hill 27599 7365, USA
    FEBS Lett 553:63-7. 2003
    ..Moreover, we observed a corresponding reduction in Akt activity, providing biochemical evidence for the development of insulin resistance in atrophic skeletal muscle...
  17. ncbi request reprint Heparin-binding epidermal growth factor cleavage mediates zinc-induced epidermal growth factor receptor phosphorylation
    Weidong Wu
    Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Am J Respir Cell Mol Biol 30:540-7. 2004
    ..Therefore, these data support an autocrine or paracrine mechanism whereby Zn(2+) induces EGFR phosphorylation through the extracellular release of EGFR ligands, which may be mediated by metalloproteinases...
  18. ncbi request reprint Insulin-independent pathways mediating glucose uptake in hindlimb-suspended skeletal muscle
    Thomas L Hilder
    Dept of Pharmacology, University of North Carolina, Chapel Hill, NC 27599 7365, USA
    J Appl Physiol 99:2181-8. 2005
    ..Taken together, these results suggest that AMPK may be an important mediator of insulin-independent glucose uptake in soleus during skeletal muscle atrophy...
  19. ncbi request reprint Regulation of equilibrative nucleoside uptake by protein kinase inhibitors
    Min Huang
    Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
    Nucleosides Nucleotides Nucleic Acids 23:1445-50. 2004
    ....
  20. ncbi request reprint Capacitative calcium entry contributes to the differential transactivation of the epidermal growth factor receptor in response to thiazolidinediones
    Brian J Dewar
    Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7365, USA
    Mol Pharmacol 72:1146-56. 2007
    ..Moreover, influx of extracellular calcium through capacitative calcium entry may be an unrecognized component that provides a mechanism for the differential induction of EGFR transactivation by these compounds...
  21. pmc Regulation of the Rho family small GTPase Wrch-1/RhoU by C-terminal tyrosine phosphorylation requires Src
    Jamie K Alan
    Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Mol Cell Biol 30:4324-38. 2010
    ..C-terminal tyrosine phosphorylation thus represents a new paradigm in posttranslational control of small GTPase localization, activation, and biological function...
  22. pmc Insulin-like growth factor-I stimulates Shc-dependent phosphatidylinositol 3-kinase activation via Grb2-associated p85 in vascular smooth muscle cells
    Yashwanth Radhakrishnan
    Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 283:16320-31. 2008
    ..We conclude that in VSMCs exposed to hyperglycemia, IGF-I stimulation of Shc facilitates the transfer of Grb2 to p85 resulting in enhanced PI3K activation and AKT phosphorylation leading to enhanced cell proliferation and migration...
  23. 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...
  24. ncbi request reprint Inhibition of nucleoside transport by p38 MAPK inhibitors
    Min Huang
    Department of Pharmacology and the Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 277:28364-7. 2002
    ..Thus these studies demonstrate that the NBMPR-sensitive equilibrative nucleoside transporters are novel and unexpected targets for the p38 MAPK inhibitors at concentrations typically used to inhibit protein kinases...
  25. ncbi request reprint Regulation of human cytidine triphosphate synthetase 1 by glycogen synthase kinase 3
    Matthew J Higgins
    Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7365, USA
    J Biol Chem 282:29493-503. 2007
    ..This is the first study to investigate the phosphorylation and regulation of human CTPS1 in human cells and suggests that GSK3 is a novel regulator of CTPS activity...
  26. ncbi request reprint Activation of mitogen-activated protein kinases by peroxisome proliferator-activated receptor ligands: an example of nongenomic signaling
    Olivia S Gardner
    Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC 27599, USA
    Mol Pharmacol 68:933-41. 2005
    ..This review will highlight recent studies that elucidate the nongenomic mechanisms of PPAR ligand-induced MAPK phosphorylation. The potential relevance of MAPK signaling in PPAR biology is also discussed...
  27. ncbi request reprint Caspase-3 dependent cleavage and activation of skeletal muscle phosphorylase b kinase
    Thomas L Hilder
    Department of Pharmacology and the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514 7365, USA
    Mol Cell Biochem 275:233-42. 2005
    ..Thus, these studies indicate that PhK may be a substrate for caspase regulation during apoptosis and suggest that activation of this enzyme may be important for the generation of ATP during programmed cell death...
  28. 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...
  29. ncbi request reprint Caspase-dependent cleavage of carbamoyl phosphate synthetase II during apoptosis
    Min Huang
    Department of Pharmacology and the Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Mol Pharmacol 61:569-77. 2002
    ..Therefore, these studies show that CAD is a novel target for caspase-dependent regulation during apoptosis and suggest that the selective inactivation of pyrimidine nucleotide synthesis accompanies the process of apoptosis...
  30. pmc Regulation of human cytidine triphosphate synthetase 2 by phosphorylation
    Karen M Kassel
    Department of Pharmacology, University of North Carolina at Chapel Hill, North Carolina 27599, USA
    J Biol Chem 285:33727-36. 2010
    ..In summary, this is the first study to characterize the kinetic properties of hCTPS1 and hCTPS2 and to identify Ser(568) as a major site of CTPS2 regulation by phosphorylation...
  31. pmc Lyn kinase-dependent regulation of miR181 and myeloid cell leukemia-1 expression: implications for drug resistance in myelogenous leukemia
    Eric I Zimmerman
    Department of Pharmacology, University of North Carolina at Chapel Hill, NC 27599 7365, USA
    Mol Pharmacol 78:811-7. 2010
    ..In summary, our results suggest that Lyn-dependent regulation of miR181 is a novel mechanism of regulating Mcl-1 expression and cell survival...
  32. pmc The human Rad9 checkpoint protein stimulates the carbamoyl phosphate synthetase activity of the multifunctional protein CAD
    Laura A Lindsey-Boltz
    Department of Biochemistry and Biophysics, and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA
    Nucleic Acids Res 32:4524-30. 2004
    ..Similar results were also obtained with an N-terminal Rad9 fragment. These findings suggest that Rad9 may play a role in ribonucleotide biosynthesis...
  33. pmc Phosphorylation of threonine 61 by cyclin a/Cdk1 triggers degradation of stem-loop binding protein at the end of S phase
    M Murat Koseoglu
    Department of Biology, Program in Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Mol Cell Biol 28:4469-79. 2008
    ..We conclude that the increase in cyclin A/Cdk1 activity at the end of S phase triggers degradation of SLBP at S/G(2)...
  34. ncbi request reprint Zn2+-induced IL-8 expression involves AP-1, JNK, and ERK activities in human airway epithelial cells
    Yu Mee Kim
    Department of Environmental Sciences and Engineering, US Environmental Protection Agency, Human Studies Facility, 104 Mason Farm Road, Chapel Hill, NC 27514, USA
    Am J Physiol Lung Cell Mol Physiol 290:L1028-35. 2006
    ..These results suggested that Zn(2+)-induced inhibition of phosphatase activity is an initiating event in MAPK and AP-1 activation that leads to enhanced IL-8 expression by human airway epithelial cells...
  35. ncbi request reprint A77 1726 induces differentiation of human myeloid leukemia K562 cells by depletion of intracellular CTP pools
    Min Huang
    Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Mol Pharmacol 62:463-72. 2002
    ..Thus these studies demonstrate an important role for CTP in regulating cell cycle progression and show that LEF is an effective inducer of tumor cell differentiation through depletion of this ribonucleotide...
  36. ncbi request reprint Mechanisms of Zn(2+)-induced signal initiation through the epidermal growth factor receptor
    James M Samet
    Human Studies Division, National Health and Environmental Effects Research Laboratory, US EPA, Research Triangle Park, NC, USA
    Toxicol Appl Pharmacol 191:86-93. 2003
    ..In summary, Zn(2+) ions induce EGFR phosphorylation in a manner dependent on c-Src but not on EGFR dimerization or EGFR kinase activation, suggesting that Zn(2+) induces EGFR transactivation by c-Src...
  37. doi request reprint An unbiased evaluation of CK2 inhibitors by chemoproteomics: characterization of inhibitor effects on CK2 and identification of novel inhibitor targets
    James S Duncan
    Department of Biochemistry, The University of Western Ontario, London, Ontario N6A 5C1, Canada
    Mol Cell Proteomics 7:1077-88. 2008
    ..The results described in the present study provide insight into the molecular mechanism of action of the inhibitors as well as drug specificity that will assist in the development of more specific next generation CK2 inhibitors...
  38. ncbi request reprint Transactivation of the EGF receptor: is the PDGF receptor an unexpected accomplice?
    Lee M Graves
    The Department of Pharmacology, and the Lineberger Comprehensive Cancer Center University of North Carolina at Chapel Hill Chapel Hill, NC 27599, USA
    Mol Interv 2:208-12. 2002

Research Grants8

  1. REGULATION OF CARBAMYL PHOSPH SYNTHETASES BY MAP KINASE
    Lee Graves; Fiscal Year: 1999
    ..Eventually with the design of potent and selective inhibitors of growth factor-activated kinase signaling pathways, novel strategies for the regulation of nucleotide metabolism and cell growth may be achieved. ..
  2. REGULATION OF CARBAMYL PHOSPH SYNTHETASES BY MAP KINASE
    Lee Graves; Fiscal Year: 2000
    ..Eventually with the design of potent and selective inhibitors of growth factor-activated kinase signaling pathways, novel strategies for the regulation of nucleotide metabolism and cell growth may be achieved. ..
  3. REGULATION OF CARBAMYL PHOSPH SYNTHETASES BY MAP KINASE
    Lee Graves; Fiscal Year: 2001
    ..Eventually with the design of potent and selective inhibitors of growth factor-activated kinase signaling pathways, novel strategies for the regulation of nucleotide metabolism and cell growth may be achieved. ..
  4. REGULATION OF CARBAMYL PHOSPH SYNTHETASES BY MAP KINASE
    Lee Graves; Fiscal Year: 2002
    ..Eventually with the design of potent and selective inhibitors of growth factor-activated kinase signaling pathways, novel strategies for the regulation of nucleotide metabolism and cell growth may be achieved. ..
  5. Regulation of Nucleoside Transporters by Protein Kinases
    Lee Graves; Fiscal Year: 2004
    ..Aim #2. Elucidate the promoter elements necessary for the expression of ENT1 and ENT2. Aim #3. Examine the specific roles of ENTs in growth, differentiation and chemosensitization . ..
  6. Regulation of Nucleoside Transporters by Protein Kinases
    Lee Graves; Fiscal Year: 2005
    ..Aim #2. Elucidate the promoter elements necessary for the expression of ENT1 and ENT2. Aim #3. Examine the specific roles of ENTs in growth, differentiation and chemosensitization . ..
  7. Regulation of Nucleoside Transporters by Protein Kinases
    Lee Graves; Fiscal Year: 2006
    ..Aim #2. Elucidate the promoter elements necessary for the expression of ENT1 and ENT2. Aim #3. Examine the specific roles of ENTs in growth, differentiation and chemosensitization . ..
  8. Regulation of Nucleoside Transporters by Protein Kinases
    Lee Graves; Fiscal Year: 2007
    ..Aim #2. Elucidate the promoter elements necessary for the expression of ENT1 and ENT2. Aim #3. Examine the specific roles of ENTs in growth, differentiation and chemosensitization . ..