Research Topics
Genomes and Genes
| John M KyriakisSummaryAffiliation: Tufts-New England Medical Center Country: USA Publications
Research Grants
| Collaborators
|
Detail Information
Publications
Inhibitors of protein kinase signaling pathways: emerging therapies for cardiovascular diseaseThomas Force
Molecular Cardiology Research Institute, Tufts New England Medical Center and Tufts University School of Medicine, Boston, Mass 02111, USA
Circulation 109:1196-205. 2004..We will specifically focus on disease states for which drug development has proceeded to the point of clinical or advanced preclinical studies...- At the crossroads: AMP-activated kinase and the LKB1 tumor suppressor link cell proliferation to metabolic regulationJohn M Kyriakis
Molecular Cardiology Research Institute, Tufts New England Medical Center, 750 Washington Street, Boston, MA 02111, USA
J Biol 2:26. 2003.... - The integration of signaling by multiprotein complexes containing Raf kinasesJohn M Kyriakis
The Molecular Cardiology Research Institute, Tufts New England Medical Center and the Department of Medicine, Tufts University School of Medicine, 750 Washington Street, Boston, MA 02111, USA
Biochim Biophys Acta 1773:1238-47. 2007..This review will focus on two signal integrating multiprotein complexes that involve Raf family kinases: the MLK3-B-Raf-Raf-1 complex and the Raf-1-Mst-2 complex... - Deficiency of the transcriptional regulator p8 results in increased autophagy and apoptosis, and causes impaired heart functionDerek K Kong
Molecular Cardiology Research Institute, Tufts Medical Center and Department of Medicine, Tufts University School of Medicine, Boston, MA 02111, USA
Mol Biol Cell 21:1335-49. 2010..Our studies provide evidence of a p8-dependent mechanism regulating autophagy by acting as FoxO3 corepressor, which may be relevant for diseases associated with dysregulated autophagy, as cardiovascular pathologies and cancer... - Mixed-lineage kinase 3 regulates B-Raf through maintenance of the B-Raf/Raf-1 complex and inhibition by the NF2 tumor suppressor proteinDeborah N Chadee
Molecular Cardiology Research Institute, Tufts New England Medical Center, Tufts University School of Medicine, 750 Washington Street, Boston, MA 02111, USA
Proc Natl Acad Sci U S A 103:4463-8. 2006..Thus, MLK3 is part of a multiprotein complex and is required for ERK activation. The levels of this complex may be negatively regulated by merlin... - Gene 33/RALT is induced by hypoxia in cardiomyocytes, where it promotes cell death by suppressing phosphatidylinositol 3-kinase and extracellular signal-regulated kinase survival signalingDazhong Xu
Molecular Cardiology Research Institute, Tufts-New England Medical Center, 750 Washington Street, Box 8486, Boston, MA 02111, USA
Mol Cell Biol 26:5043-54. 2006..Gene 33 levels are also strikingly increased in myocardial ischemic injury and infarction. Our results identify a new role for Gene 33 as a component in the molecular pathophysiology of ischemic injury... - Dissection of a signaling pathway by which pathogen-associated molecular patterns recruit the JNK and p38 MAPKs and trigger cytokine releaseJian Zhong
Molecular Cardiology Research Institute, Department of Medicine, Tufts New England Medical Center and the Boston, Massachusetts 02111, USA
J Biol Chem 282:24246-54. 2007..Our results define a signaling pathway whereby PAMPs can trigger MAPK activation and gene expression... - Helix-loop-helix protein p8, a transcriptional regulator required for cardiomyocyte hypertrophy and cardiac fibroblast matrix metalloprotease inductionSandro Goruppi
Molecular Cardiology Research Institute, Tufts New England Medical Center, 750 Washington Street, Box 8486, Boston, MA 02111, USA
Mol Cell Biol 27:993-1006. 2007..Our results identify an unexpectedly broad involvement for p8 in key cellular events linked to cardiomyocyte hypertrophy and cardiac fibroblast MMP production, both of which occur in heart failure... - Decreased metalloprotease 9 induction, cardiac fibrosis, and higher autophagy after pressure overload in mice lacking the transcriptional regulator p8Serban P Georgescu
Molecular Cardiology Research Institute, Tufts Medical Center, Department of Medicine, Tufts University School of Medicine, Boston, MA 02111, USA
Am J Physiol Cell Physiol 301:C1046-56. 2011..These findings suggest a role for p8 in regulating in vivo key signaling pathways involved in the pathogenesis of heart failure... - GCK is essential to systemic inflammation and pattern recognition receptor signaling to JNK and p38Jian Zhong
The Molecular Cardiology Research Institute, and Department of Medicine, Tufts University School of Medicine, Boston, MA 02111, USA
Proc Natl Acad Sci U S A 106:4372-7. 2009..Extracellular signal-regulated kinase (ERK) and nuclear factor-kappaB (NF-kappaB) activation are largely unaffected. Thus, GCK is an essential PAMP effector coupling JNK and p38, but not ERK or NF-kappaB to systemic inflammation... - Mammalian Ste20-like kinase (Mst2) indirectly supports Raf-1/ERK pathway activity via maintenance of protein phosphatase-2A catalytic subunit levels and consequent suppression of inhibitory Raf-1 phosphorylationGeoffrey K Kilili
Molecular Cardiology Research Institute, Tufts Medical Center, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachusetts 02111, USA
J Biol Chem 285:15076-87. 2010..Our studies reveal a more complex role for Mst2 than previously thought. The Mst2 --> LATS1/2 pathway, by maintaining PP2A-C levels, may, in some situations, positively affect mitogenic signaling... - Germinal center kinase is required for optimal Jun N-terminal kinase activation by Toll-like receptor agonists and is regulated by the ubiquitin proteasome system and agonist-induced, TRAF6-dependent stabilizationJian Zhong
Molecular Cardiology Research Institute Tufts New England Medical Center, 750 Washington St, Box 8486, Boston, MA 02111, USA
Mol Cell Biol 24:9165-75. 2004..Our results identify a physiologic function and unexpected mode of regulation for GCK... - MLK3 is required for mitogen activation of B-Raf, ERK and cell proliferationDeborah N Chadee
The Molecular Cardiology Research Institute, Department of Medicine, Tufts New England Medical Center and the Department of Medicine, Tufts University School of Medicine, 750 Washington Street, Box 8486, Boston, MA 02111, USA
Nat Cell Biol 6:770-6. 2004..The proliferation of tumour cells containing activating B-raf or raf-1 mutations was unaffected by silencing mlk3. Our results define an unexpected role for MLK3 in mitogen regulation of B-Raf, ERK and cell proliferation... - A novel role for mixed lineage kinase 3 (MLK3) in B-Raf activation and cell proliferationDeborah N Chadee
The Molecular Cardiology Research Institute, Tufts New England Medical Center, Boston, Massachusetts 02111, USA
Cell Cycle 3:1227-9. 2004..Accordingly, targeting MLK3 could be beneficial to the treatment of tumors with activated receptor tyrosine kinase or ras mutations, and to the treatment of NF1 or NF2 tumors... - Gene 33 is an endogenous inhibitor of epidermal growth factor (EGF) receptor signaling and mediates dexamethasone-induced suppression of EGF functionDazhong Xu
Molecular Cardiology Research Institute, Tufts New England Medical Center and Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
J Biol Chem 280:2924-33. 2005..Our results also indicate a role for Gene 33 in the suppression, by Dex, of EGF signaling pathways. We propose that Gene 33 may function in the cross-talk between EGF signaling and other mitogenic and/or stress signaling pathways... - The pro-hypertrophic basic helix-loop-helix protein p8 is degraded by the ubiquitin/proteasome system in a protein kinase B/Akt- and glycogen synthase kinase-3-dependent manner, whereas endothelin induction of p8 mRNA and renal mesangial cell hypertrophy Sandro Goruppi
Molecular Cardiology Research Institute, Tufts New England Medical Center and the Department of Medicine, Tufts University School of Medicine, 750 Washington Street, Boston, MA 02111, USA
J Biol Chem 279:20950-8. 2004..Thus, p8 levels in the cell are likely maintained by a balance between signal-dependent transcriptional induction and proteolysis... - Activation of SAPKs/JNKs and p38s in vitroJohn M Kyriakis
Molecular Cardiology Research Institute, Tufts-New England Medical Center, Boston, MA, USA
Methods Mol Biol 250:61-88. 2004 - Phosphatidylinositol 3'-kinase-dependent activation of renal mesangial cell Ki-Ras and ERK by advanced glycation end productsDazhong Xu
Molecular Cardiology Research Institute, New England Medical Center and the Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
J Biol Chem 278:39349-55. 2003..Thus, AGEs signal to Ki-Ras and ERK through reactive oxygen species-dependent activation of PI3K... - Signaling pathways and late-onset gene induction associated with renal mesangial cell hypertrophySandro Goruppi
Diabetes Research Laboratory, Department of Medicine, Massachusetts General Hospital, Charlestown, MA 02129, USA
EMBO J 21:5427-36. 2002..Small interfering RNA (siRNA)-mediated RNA interference indicates that p8 is required for endothelin-induced hypertrophy. Thus, p8 is a novel marker for diabetic renal hypertrophy... - Glucocorticoid receptor-JNK interaction mediates inhibition of the JNK pathway by glucocorticoidsAlejandra Bruna
, , Universitat de Barcelona, E-08028 Barcelona, Spain
EMBO J 22:6035-44. 2003..In this regard, chromatin immunoprecipitation assays show that GC-induced GR-JNK association correlates with an increase in the loading of inactive JNK on the AP-1-bound response elements of the c-jun gene... - Direct activation of mitogen-activated protein kinase kinase kinase MEKK1 by the Ste20p homologue GCK and the adapter protein TRAF2Deborah N Chadee
Diabetes Research Laboratory, Medical Services, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
Mol Cell Biol 22:737-49. 2002..These results represent the first activation of MEKK1 in vitro using purified proteins and suggest a mechanism for MEKK1 activation involving induced oligomerization and consequent autophosphorylation mediated by upstream proteins... - Phosphorylation of threonine 276 in Smad4 is involved in transforming growth factor-beta-induced nuclear accumulationBernard A J Roelen
Program in Membrane Biology and Renal Unit, Massachusetts General Hospital, and Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA
Am J Physiol Cell Physiol 285:C823-30. 2003..Our results suggest that MAP kinase can phosphorylate Thr276 of Smad4 and that phosphorylation can lead to enhanced TGF-beta-induced nuclear accumulation and, as a consequence, enhanced transcriptional activity of Smad4... - Defective Rac-mediated proliferation and survival after targeted mutation of the beta1 integrin cytodomainEmilio Hirsch
Dipartimento di Genetica, Biologia, e Biochimica, Universita di Torino, 10126 Torino, Italy
J Cell Biol 157:481-92. 2002..Altogether, our data provide the evidence for an epistatic interaction between the beta1 integrin cytoplasmic domain and Rac, and indicate that this anchorage-dependent signaling pathway is crucial for cell growth control...
Research Grants
- MOLECULAR MEDIATORS OF DIABETIC RENAL HYPERTROPHYJohn Kyriakis; Fiscal Year: 2002..These studies, they hope, will expand our knowledge of signal transduction in the diabetic kidney and contribute to the development of novel treatments for diabetic nephropathy using signaling components as targets. ..
- Typhoon 9410 Variable Mode ImagerJohn Kyriakis; Fiscal Year: 2005..abstract_text> ..