Research Topics
Genomes and Genes
| Gary L JohnsonSummaryAffiliation: University of North Carolina Country: USA Publications
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Detail Information
Publications
Sequence patches on MAPK surfaces define protein-protein interactionsGary L Johnson
Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599 7365, USA
Genome Biol 10:222. 2009..Recent studies on the modularity of mitogen-activated protein kinases show how redesigning 'surface patches' on a protein can change the topology of a signaling network...- Defining MAPK interactomesGary L Johnson
Department of Pharmacology, University of North Carolina, Chapel Hill, 27599, United States
ACS Chem Biol 6:18-20. 2011..This discovery process provides a rich data and reagent resource for defining complexities of protein networks involving MAPKs and control of cellular physiology... - 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... - Trophoblast stem cell maintenance by fibroblast growth factor 4 requires MEKK4 activation of Jun N-terminal kinaseAmy N Abell
Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 7365, USA
Mol Cell Biol 29:2748-61. 2009..Our results define MEKK4 as a signaling hub for FGF4 activation of JNK that is required for maintenance of TS cells in an undifferentiated state... - Rho kinase inhibition rescues the endothelial cell cerebral cavernous malformation phenotypeAsya L Borikova
Department of Pharmacology and Lineberger Comprehensive Cancer Center, School of Dentistry, University of North Carolina, Chapel Hill, North Carolina 27599, USA
J Biol Chem 285:11760-4. 2010..The results define Rho kinase as a therapeutic target to rescue endothelial cells from loss of CCM protein function... - 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... - Tracking the intermediate stages of epithelial-mesenchymal transition in epithelial stem cells and cancerNicole Vincent Jordan
Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA
Cell Cycle 10:2865-73. 2011..This intersection between EMT and stemness in TS cells and claudin-low metastatic breast cancer demonstrates the usefulness of developmental EMT systems to understand EMT in cancer... - PB1 domain interaction of p62/sequestosome 1 and MEKK3 regulates NF-kappaB activationKazuhiro Nakamura
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 285:2077-89. 2010..The rear end acidic cluster of the p62 PB1 domain is used to organize cytosolic aggregates or speckles-associated TRAF6-p62-MEKK3 complex for control of NF-kappaB activation... - 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... - 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... - 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... - 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... - Defining the functional domain of programmed cell death 10 through its interactions with phosphatidylinositol-3,4,5-trisphosphateChristopher F Dibble
Department of Pharmacology, School of Medicine, and the Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, United States of America
PLoS ONE 5:e11740. 2010..Combining computational modeling and biological data, we propose that the CCM protein complex functions in the PI3K signaling pathway through the interaction between PDCD10 and PtdIns(3,4,5)P3... - 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... - Proteomic identification of the cerebral cavernous malformation signaling complexThomas L Hilder
Department of Pharmacology and the Lineberger Comprehensive Cancer Center, School of Dentistry, University of North Carolina, Chapel Hill, CB 7365, Chapel Hill, North Carolina 27599 7365, USA
J Proteome Res 6:4343-55. 2007..The findings define the targeting of the CCM complex to membranes and to proteins regulating trafficking and the cytoskeleton... - 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... - 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.... - MAP3K4/CBP-regulated H2B acetylation controls epithelial-mesenchymal transition in trophoblast stem cellsAmy N Abell
Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC 27599 7365, USA
Cell Stem Cell 8:525-37. 2011..Taken together, our data define an epigenetic switch that maintains the epithelial phenotype in TS cells and reveals previously unrecognized genes potentially contributing to breast cancer... - 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... - 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... - In vivo profiling endogenous interactions with knock-out in mammalian cellsLing Xie
Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina, 120 Mason Farm Road, Genetic Medicine, Ste 3010, Campus Box No 7260, Chapel Hill, North Carolina 27599 7260, USA
Anal Chem 81:1411-7. 2009..Because of the availability of a large library of knockout mice models with various target proteins of biological interests our method is generally applicable to screen any endogenous target-specific PPIs of physiological relevance... - 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... - 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... - Activity assays for extracellular signal-regulated kinase 5Kazuhiro Nakamura
Department of Pharmacology and Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina, Chapel Hill, NC, USA
Methods Mol Biol 661:91-106. 2010..ERK5 is also critical for maintenance of vascular integrity and endothelial cell survival. In this chapter, we define methods used to measure the activation of ERK5 using different biochemical and cell-based assays... - Cerebral cavernous malformation 2 protein promotes smad ubiquitin regulatory factor 1-mediated RhoA degradation in endothelial cellsLisa E S Crose
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 284:13301-5. 2009.... - 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.... - 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... - 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... - 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... - Laser-scanning velocimetry: a confocal microscopy method for quantitative measurement of cardiovascular performance in zebrafish embryos and larvaeMichael H Malone
Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
BMC Biotechnol 7:40. 2007..A laser scan line placed parallel to the path of blood in the dorsal aorta measures blood cell velocity, from which cardiac output and indices of vascular resistance and contractility are calculated... - 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... - 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... - 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.... - 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... - Efficiently identifying genome-wide changes with next-generation sequencing dataWeichun Huang
Biostatistics Branch, National Institute of Environmental Health Sciences, RTP, NC 27709, USA
Nucleic Acids Res 39:e130. 2011..In particular, we show that our novel and robust 'parsimony' normalization method is superior to the widely-used 'tagRatio' method. Our software EpiCenter is freely available to the public... - 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... - Data-driven modeling of cellular stimulation, signaling and output response in RAW 264.7 cellsYang Wu
Joint Department of Biomedical Engineering, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
J Mol Signal 3:11. 2008..Of particular interest is the establishment of methods for the analysis of cellular-level input-output signaling relationships that have been characterized over time... - 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...