Research Topics
Species | Gary JohnsonSummaryAffiliation: University of Colorado Health Sciences Center Country: USA Publications
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Publications
Signal transduction. Scaffolding proteins--more than meets the eyeGary Johnson
Department of Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262, USA
Science 295:1249-50. 2002- Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinasesGary L Johnson
Department of Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262, USA
Science 298:1911-2. 2002..The p38 MAPKs are activated by inflammatory cytokines and environmental stresses and may contribute to diseases like asthma and autoimmunity... - Combined use of oligonucleotide and tissue microarrays identifies cancer/testis antigens as biomarkers in lung carcinomaMichio Sugita
Department of Pathology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
Cancer Res 62:3971-9. 2002.... 
Bradykinin antagonist dimer, CU201, inhibits the growth of human lung cancer cell lines by a "biased agonist" mechanismDaniel Chan
Lung Cancer Program, University of Colorado Cancer Center, Denver, CO 80262, USA
Proc Natl Acad Sci U S A 99:4608-13. 2002..CU201 and similar compounds offer hope of becoming a new form of targeted therapy for tumors with neuroendocrine properties...- ZD1839, a selective epidermal growth factor receptor tyrosine kinase inhibitor, alone and in combination with radiation and chemotherapy as a new therapeutic strategy in non-small cell lung cancerDavid Raben
Department of Radiation Oncology, University of Colorado Comprehensive Cancer Center, Denver, CO 80010-0510, USA
Semin Oncol 29:37-46. 2002..Future studies will certainly combine ZD1839 with chemotherapy or radiation. ZD1839 also may be effective as a chemoprevention agent because premalignant lesions often overexpress epidermal growth factor receptor... - Ablation of MEK kinase 1 suppresses intimal hyperplasia by impairing smooth muscle cell migration and urokinase plasminogen activator expression in a mouse blood-flow cessation modelYan Li
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
Circulation 111:1672-8. 2005..Although MEK kinase 1 (MEKK1) has been shown to regulate cell migration and urokinase plasminogen activator (uPA) expression, the precise role of MEKK1 in this process remains unknown... - MEKK1 regulates the AP-1 dimer repertoire via control of JunB transcription and Fra-2 protein stabilityBruce D Cuevas
Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599 7365, USA
Oncogene 24:801-9. 2005..Controlling the repertoire of a transcription factor complex is a newly defined function for an MAPK kinase kinase... - JNK regulates the release of proapoptotic mitochondrial factors in reovirus-infected cellsPenny Clarke
Dept of Neurology B 182, University of Colorado Health Sciences Center, 4200 East 9th Ave, Denver, CO 80262, USA
J Virol 78:13132-8. 2004..This is the first report demonstrating that JNK is associated with regulation of mitochondrial pathways of apoptosis following viral infection... - MEKK2 regulates the coordinate activation of ERK5 and JNK in response to FGF-2 in fibroblastsKamala Kesavan
Department of Pharmacology and University of Colorado Cancer Center, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
J Cell Physiol 199:140-8. 2004..Bacterial lipopolysaccharide (LPS) and TNFalpha neither activate ERK5 nor require MEKK2 for JNK activation, demonstrating specificity of MEKK2 in FGF-2 receptor signaling and control of cytokine gene expression... - Rac2D57N, a dominant inhibitory Rac2 mutant that inhibits p38 kinase signaling and prevents surface ruffling in bone-marrow-derived macrophagesAmy N Abell
Department of Pharmacology, University of Colorado Health Sciences Center, 4200 East Ninth Ave, Denver, CO 80262, USA
J Cell Sci 117:243-55. 2004..Enhanced binding of Rac2D57N to its upstream regulators would inhibit Rac-dependent effects on actin cytoskeletal dynamics and p38 kinase signaling... - Rac-MEKK3-MKK3 scaffolding for p38 MAPK activation during hyperosmotic shockMark T Uhlik
Department of Pharmacology and the Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine Chapel Hill, NC 27599 7365, USA
Nat Cell Biol 5:1104-10. 2003..The Rac-OSM-MEKK3-MKK3 complex is the mammalian counterpart of the CDC42-STE50-STE11-Pbs2 complex in Saccharomyces cerevisiae that is required for the regulation of p38 activity... - MEF2C regulates c-Jun but not TNF-alpha gene expression in stimulated mast cellsXudong Wei
Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA
Eur J Immunol 33:2903-9. 2003.... - Roles for TAB1 in regulating the IL-1-dependent phosphorylation of the TAB3 regulatory subunit and activity of the TAK1 complexHeidi Mendoza
MRC Protein Phosphorylation Unit, University of Dundee, Dundee DD1 5EH, Scotland, UK
Biochem J 409:711-22. 2008.... - CCM1 and CCM2 protein interactions in cell signaling: implications for cerebral cavernous malformations pathogenesisJon S Zawistowski
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
Hum Mol Genet 14:2521-31. 2005..These data indicate that the genetic heterogeneity observed in familial CCM may reflect mutation of different molecular members of a coordinated signaling complex... - Hyperosmotic induction of mitogen-activated protein kinase scaffoldingThomas L Hilder
Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Methods Enzymol 428:297-312. 2007.... - Integrated activation of MAP3Ks balances cell fate in response to stressAnn M Winter Vann
Department of Pharmacology, 1108 Mary Ellen Jones Bldg, Campus Box 7365, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 7365, USA
J Cell Biochem 102:848-58. 2007..The interrelationships among different stressors are discussed, with an emphasis on how the balance of signaling through MAP3Ks controls the MAPK response to determine cell fate... - MEKK4 stimulation of p38 and JNK activity is negatively regulated by GSK3betaAmy N Abell
Department of Pharmacology and the Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 7365, USA
J Biol Chem 282:30476-84. 2007..Thus, control of MEKK4 dimerization is regulated both positively and negatively by its interaction with specific proteins... - The c-jun kinase/stress-activated pathway: regulation, function and role in human diseaseGary L Johnson
University of North Carolina at Chapel Hill, Department of Pharmacology, and Lineberger Comprehensive Cancer Center, 31 331 LCC Chapel Hill, NC 27599, USA
Biochim Biophys Acta 1773:1341-8. 2007..In this review, we present our current understanding of JNK regulation and their involvement in homeostasis and dysregulation in human disease... - MEKK1 mediates the ubiquitination and degradation of c-Jun in response to osmotic stressYan Xia
Department of Neuro Oncology, Unit 1002, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
Mol Cell Biol 27:510-7. 2007..Furthermore, apoptosis induced by osmotic stress was suppressed by overexpression of c-Jun, indicating that the downregulation of c-Jun promotes apoptosis... - Analysis of orthologous gene expression between human pulmonary adenocarcinoma and a carcinogen-induced murine modelRobert S Stearman
Department of Medicine Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, USA
Am J Pathol 167:1763-75. 2005..Thus, the A/J mouse-urethane model reflects significant molecular details of human lung AC, and comparison of changes in orthologous gene expression may provide novel insights into lung carcinogenesis... - Ablation of MEKK4 kinase activity causes neurulation and skeletal patterning defects in the mouse embryoAmy N Abell
Department of Pharmacology, University of North Carolina, Chapel Hill, 27599 7365, USA
Mol Cell Biol 25:8948-59. 2005..Together, these data demonstrate MEKK4 regulation of p38 and that substrates downstream of p38 control cellular homeostasis. The findings are the first demonstration that MEKK4-regulated p38 activity is critical for neurulation... - MEKK4 is an effector of the embryonic TRAF4 for JNK activationAmy N Abell
Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 7365, USA
J Biol Chem 280:35793-6. 2005..The findings identify MEKK4 as the MAPK kinase kinase for TRAF4 regulation of the JNK pathway... - PB1 domains of MEKK2 and MEKK3 interact with the MEK5 PB1 domain for activation of the ERK5 pathwayKazuhiro Nakamura
Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 7365, USA
J Biol Chem 278:36989-92. 2003..The free PB1 domain of MEKK2 or MEKK3 functions effectively to inhibit the ERK5 pathway but not the p38 or JNK pathways, demonstrating the specific and unique requirement of the MEKK2 and MEKK3 PB1 domain in regulating ERK5 activation... - The MEKK1-JNK pathway plays a protective role in pressure overload but does not mediate cardiac hypertrophyJunichi Sadoshima
Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103, USA
J Clin Invest 110:271-9. 2002..MEKK1 also prevents apoptosis and inflammation, thereby protecting against heart failure and sudden death following cardiac pressure overload... - MEKK1 is essential for cardiac hypertrophy and dysfunction induced by GqTetsuo Minamino
Center for Cardiovascular Development and The DeBakey Heart Center, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
Proc Natl Acad Sci U S A 99:3866-71. 2002..Thus, MEKK1 mediates cardiac hypertrophy induced by Galphaq in vivo and is a logical target for drug development in heart disease involving this pathway... - Reovirus-induced alterations in gene expression related to cell cycle regulationGeorge J Poggioli
Department of Microbiology, University of Colorado Health Sciences Center, Denver, Colorado 80220, USA
J Virol 76:2585-94. 2002..A hypothetical model describing serotype 3 reovirus-induced inhibition of cdc2 kinase is presented, and reovirus-induced perturbations of the G(1)-to-S, G(2)-to-M, and mitotic spindle checkpoints are discussed... - Mixed-lineage kinase control of JNK and p38 MAPK pathwaysKathleen A Gallo
Department of Physiology, Michigan State University, East Lansing, Michigan 48824, USA
Nat Rev Mol Cell Biol 3:663-72. 2002..The Drosophila MLK Slipper regulates JNK to control dorsal closure during embryonic morphogenesis. In mammalian cells, MLKs are implicated in the control of apoptosis and are potential drug targets for many neurodegenerative diseases... - TRAIL and inhibitors of apoptosis are opposing determinants for NF-kappaB-dependent, genotoxin-induced apoptosis of cancer cellsAaron C Spalding
Department of Pharmacology, University of Colorado Cancer Center, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, Colorado, CO 80262, USA
Oncogene 21:260-71. 2002..These findings demonstrate that TRAIL signaling via its death receptors is a significant contributor to genotoxin-induced apoptosis in human epithelial carcinomas... - MEKK1-induced apoptosis requires TRAIL death receptor activation and is inhibited by AKT/PKB through inhibition of MEKK1 cleavageAndrea H Bild
Department of Pharmacology, University of Colorado, 2400 East Ninth Street, Denver, Colorado, CO 80262, USA
Oncogene 21:6649-56. 2002..Thus, MEKK1-induced apoptosis requires TRAIL death receptor activation and is blocked by AKT through inhibition of MEKK1 cleavage... - Apoptosis stimulated by the 91-kDa caspase cleavage MEKK1 fragment requires translocation to soluble cellular compartmentsThomas K Schlesinger
Institute of Cellular Biology and Morphology, University of Lausanne, 1005 Lausanne, Switzerland
J Biol Chem 277:10283-91. 2002.... - Ubiquitylation of MEKK1 inhibits its phosphorylation of MKK1 and MKK4 and activation of the ERK1/2 and JNK pathwaysJames A Witowsky
Department of Pharmacology, University of Colorado Health Sciences Center and University of Colorado Cancer Center, Denver, Colorado 80262, USA
J Biol Chem 278:1403-6. 2003..MEKK1 ubiquitylation represents a mechanism for inhibiting the ability of a protein kinase to phosphorylate substrates and regulate downstream signaling pathways... - MEKK1 is required for inducible urokinase-type plasminogen activator expressionJames Witowsky
Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
J Biol Chem 278:5941-6. 2003..Importantly, disrupted expression of MEKK2, a related MAPK kinase kinase, had no effect on uPA activity. Therefore, we conclude that MEKK1 expression is required for PMA- or FGF-2-induced signals to control uPA expression and function... - MEK kinase 2 and the adaptor protein Lad regulate extracellular signal-regulated kinase 5 activation by epidermal growth factor via SrcWeiyong Sun
Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
Mol Cell Biol 23:2298-308. 2003.... - Role of the amino-terminal domains of MEKKs in the activation of NF kappa B and MAPK pathways and in the regulation of cell proliferation and apoptosisChristelle Bonvin
Institute of Cellular Biology and Morphology, Lausanne University, Lausanne, Switzerland
Cell Signal 14:123-31. 2002..Our data show that the N-terminal domain of the MEKKs determines the specificity and the strength of activation of various intracellular signaling pathways and cellular responses... - MEKK1 regulates calpain-dependent proteolysis of focal adhesion proteins for rear-end detachment of migrating fibroblastsBruce D Cuevas
Department of Pharmacology, Craniofacial Biology, University of Colorado Health Sciences Center, Denver, CO 80262, USA
EMBO J 22:3346-55. 2003..Inhibition of ERK1/2 or calpain, but not of JNK, mimics MEKK1 deficiency. Therefore, MEKK1 regulates calpain-mediated substratum release of migrating fibroblasts... - Inhibition of Src family kinases blocks epidermal growth factor (EGF)-induced activation of Akt, phosphorylation of c-Cbl, and ubiquitination of the EGF receptorC Kenneth Kassenbrock
Department of Pathology, University of Colorado Health Sciences Center, Denver 80262, USA
J Biol Chem 277:24967-75. 2002..PP1 treatment blocks EGF-induced activation of the anti-apoptotic protein kinase Akt suggesting that Src may regulate activation of Akt, perhaps by a Src --> c-Cbl --> phosphatidylinositol 3'-kinase --> Akt pathway... - Activation of chymotrypsin-like serine protease(s) during apoptosis detected by affinity-labeling of the enzymatic center with fluoresceinated inhibitorJerzy Grabarek
Brander Cancer Research Institute, New York Medical College, Valhalla, NY 10595, USA
Int J Oncol 20:225-33. 2002..Ser-protease(s) was different. Our approach makes it possible to simultaneously monitor activation of caspases and Ser proteases in the same live cells that are induced to apoptosis... - Noncanonical function of MEKK2 and MEK5 PB1 domains for coordinated extracellular signal-regulated kinase 5 and c-Jun N-terminal kinase signalingKazuhiro Nakamura
Department of Pharmacology, 1108 Mary Ellen Jones Building, University of North Carolina School of Medicine, Chapel Hill, NC 27599 7365, USA
Mol Cell Biol 27:4566-77. 2007..The findings define how the MEKK2 and MEK5 PB1 domains are uniquely used for differential binding of two mitogen-activated protein kinase kinases, MEK5 and MKK7, for the coordinated control of ERK5 and c-Jun N-terminal kinase activation... - PB1 domain-dependent signaling complex is required for extracellular signal-regulated kinase 5 activationKazuhiro Nakamura
Department of Pharmacology, CB#7365, 1108 Mary Ellen Jones Building, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7365, USA
Mol Cell Biol 26:2065-79. 2006..The MEK5 PB1 domain confers stringent MAP3K regulation of ERK5 relative to more promiscuous MAP3K control of ERK1/2, JNK, and p38... - Kinetics of HL-60 cell entry to apoptosis during treatment with TNF-alpha or camptothecin assayed by the stathmo-apoptosis methodPiotr Smolewski
Brander Cancer Research Institute, New York Medical College, 19 Bradhurst Avenue, Suite 2400, Hawthorne, NY 10532, USA
Cytometry 47:143-9. 2002..2% of cells per hour. CONCLUSIONS: This approach provides a means for measuring the kinetics of cell entrance to apoptosis (caspase activation) in large populations of cells in relation to the cell-cycle position... - Detection of caspases activation in situ by fluorochrome-labeled inhibitors of caspases (FLICA)Zbigniew Darzynkiewicz
Brander Cancer Research Institute, New York Medical College, Valhalla, NY, USA
Methods Mol Biol 203:289-99. 2002 - Reovirus-induced alteration in expression of apoptosis and DNA repair genes with potential roles in viral pathogenesisRoberta L Debiasi
Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
J Virol 77:8934-47. 2003..This provides the first comparative analysis of altered gene expression after infection with viruses of differing apoptotic phenotypes and provides insight into pathogenic mechanisms of virus-induced disease... - MAPK kinase kinases (MKKKs) as a target class for small-molecule inhibition to modulate signaling networks and gene expressionGary 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.... - Wiring diagrams of MAPK regulation by MEKK1, 2, and 3Mark T Uhlik
Department of Pharmacology, University of North Carolina School of Medicine, 1108 Mary Ellen Jones Building, CB# 7365, Chapel Hill, NC 27599, USA
Biochem Cell Biol 82:658-63. 2004..We propose that signal transduction network wiring diagrams are valuable tools for hypothesis building and filtering physiologically relevant phenotypic responses from less connected protein relations in the regulation of MAPK pathways... - Structural and evolutionary division of phosphotyrosine binding (PTB) domainsMark T Uhlik
Department of Pharmacology and University of North Carolina School of Medicine, 1108 Mary Ellen Jones Building, Campus Box 7365, Chapel Hill, NC 27599-7365, USA
J Mol Biol 345:1-20. 2005..The signaling complexes organized by PTB domain encoded proteins are largely unknown and represents an important challenge in systems biology for the future... - Sequential activation of caspases and serine proteases (serpases) during apoptosisJerzy Grabarek
Brander Cancer Research Institute; New York Medical College; Valhalla, New York 10595, USA
Cell Cycle 1:124-31. 2002..Their apparent molecular weight (62-65 kD) suggests that they are novel enzymes... - CP-64131, an aminobenzazepine with cytokine-like properties, stimulates human neutrophil functions through the p38-MAPK pathwayMarsha S Anderson
Bonfils Blood Center, 717 Yosemite Street, Denver, CO 80230, USA
J Leukoc Biol 76:477-83. 2004..CP has the ability to activate specific MAPK pathways in different cell types and should prove to be an effective agonist in combination with inhibitors to study biological responses regulated by MAPKs... - The in vitro production and characterization of neutrophils from embryonic stem cellsJonathan G Lieber
National Jewish Medical and Research Center, 1400 Jackson St, Denver, CO 80206, USA
Blood 103:852-9. 2004..During the differentiation of these ES-derived neutrophils, regional areas of neutrophil production can be identified that have been designated as neutrophil generating regions (NGRs)... 
Homogeneous time-resolved fluorescence resonance energy transfer assay for measurement of Phox/Bem1p (PB1) domain heterodimerizationKazuhiro Nakamura
Department of Pharmacology and the Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 7365, USA
J Biomol Screen 13:396-405. 2008..Disruption of PB1 domain interactions represents a novel approach for selectively regulating the ERK5 signaling pathway independent of kinase active site-directed adenosine triphosphate competitive inhibitors...