Michael Karin

Summary

Affiliation: University of California
Country: USA

Publications

  1. ncbi request reprint CK2 Is a C-Terminal IkappaB Kinase Responsible for NF-kappaB Activation during the UV Response
    Tomohisa Kato
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Mol Cell 12:829-39. 2003
  2. ncbi request reprint From JNK to pay dirt: jun kinases, their biochemistry, physiology and clinical importance
    Michael Karin
    Department of Pharmacology, School of Medicine, University of California, San Diego, California 92093 0723, USA
    IUBMB Life 57:283-95. 2005
  3. pmc Tobacco smoke promotes lung tumorigenesis by triggering IKKbeta- and JNK1-dependent inflammation
    Hiroyuki Takahashi
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, School of Medicine, La Jolla, CA 92093 0723, USA
    Cancer Cell 17:89-97. 2010
  4. pmc NF-kappaB as a critical link between inflammation and cancer
    Michael Karin
    Department of Pharmacology and Pathology, Moores Cancer Canter, UCSD School of Medicine, La Jolla, California 92093 0723, USA
    Cold Spring Harb Perspect Biol 1:a000141. 2009
  5. pmc Different modes of ubiquitination of the adaptor TRAF3 selectively activate the expression of type I interferons and proinflammatory cytokines
    Ping Hui Tseng
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Department of Pathology, School of Medicine, University of California San Diego, La Jolla, California, USA
    Nat Immunol 11:70-5. 2010
  6. ncbi request reprint IKKbeta couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis
    Shin Maeda
    Laboratory of Gene Regulation and Signal Transduction, University of California, San Diego, 9500 Gilman Drive MC 0723, La Jolla, California 92093, USA
    Cell 121:977-90. 2005
  7. pmc Essential cytoplasmic translocation of a cytokine receptor-assembled signaling complex
    Atsushi Matsuzawa
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0723, USA
    Science 321:663-8. 2008
  8. pmc Hepatocyte necrosis induced by oxidative stress and IL-1 alpha release mediate carcinogen-induced compensatory proliferation and liver tumorigenesis
    Toshiharu Sakurai
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    Cancer Cell 14:156-65. 2008
  9. pmc IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer
    Sergei Grivennikov
    Laboratory of Gene Regulation and Signal Transduction, UCSD School of Medicine, University of California San Diego, La Jolla, CA 92093 0723, USA
    Cancer Cell 15:103-13. 2009
  10. pmc I{kappa}B kinase (IKK){beta}, but not IKK{alpha}, is a critical mediator of osteoclast survival and is required for inflammation-induced bone loss
    Maria Grazia Ruocco
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    J Exp Med 201:1677-87. 2005

Detail Information

Publications67

  1. ncbi request reprint CK2 Is a C-Terminal IkappaB Kinase Responsible for NF-kappaB Activation during the UV Response
    Tomohisa Kato
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Mol Cell 12:829-39. 2003
    ..Inhibition of this pathway prevents UV-induced IkappaBalpha degradation and increases UV-induced cell death. Thus, the p38-CK2-NF-kappaB axis is an important component of the mammalian UV response...
  2. ncbi request reprint From JNK to pay dirt: jun kinases, their biochemistry, physiology and clinical importance
    Michael Karin
    Department of Pharmacology, School of Medicine, University of California, San Diego, California 92093 0723, USA
    IUBMB Life 57:283-95. 2005
    ..Importantly, the JNKs have become prime targets for drug development in several important clinical areas, including: inflammation, diabetes, and cancer...
  3. pmc Tobacco smoke promotes lung tumorigenesis by triggering IKKbeta- and JNK1-dependent inflammation
    Hiroyuki Takahashi
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, School of Medicine, La Jolla, CA 92093 0723, USA
    Cancer Cell 17:89-97. 2010
    ..Tumor promotion is due to induction of inflammation that results in enhanced pneumocyte proliferation and is abrogated by IKKbeta ablation in myeloid cells or inactivation of JNK1...
  4. pmc NF-kappaB as a critical link between inflammation and cancer
    Michael Karin
    Department of Pharmacology and Pathology, Moores Cancer Canter, UCSD School of Medicine, La Jolla, California 92093 0723, USA
    Cold Spring Harb Perspect Biol 1:a000141. 2009
    ..Most importantly, through its ability to up-regulate the expression of tumor promoting cytokines, such as IL-6 or TNF-alpha, and survival genes, such as Bcl-X(L), NF-kappaB provides a critical link between inflammation and cancer...
  5. pmc Different modes of ubiquitination of the adaptor TRAF3 selectively activate the expression of type I interferons and proinflammatory cytokines
    Ping Hui Tseng
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Department of Pathology, School of Medicine, University of California San Diego, La Jolla, California, USA
    Nat Immunol 11:70-5. 2010
    ..Inhibition of degradative ubiquitination of TRAF3 prevented the expression of all proinflammatory cytokines without affecting the interferon response...
  6. ncbi request reprint IKKbeta couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis
    Shin Maeda
    Laboratory of Gene Regulation and Signal Transduction, University of California, San Diego, 9500 Gilman Drive MC 0723, La Jolla, California 92093, USA
    Cell 121:977-90. 2005
    ..IKKbeta, therefore, orchestrates inflammatory crosstalk between hepatocytes and hematopoietic-derived cells that promotes chemical hepatocarcinogenesis...
  7. pmc Essential cytoplasmic translocation of a cytokine receptor-assembled signaling complex
    Atsushi Matsuzawa
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0723, USA
    Science 321:663-8. 2008
    ..This two-stage signaling mechanism may apply to other innate immune receptors, accounting for spatial and temporal separation of MAPK and IKK signaling...
  8. pmc Hepatocyte necrosis induced by oxidative stress and IL-1 alpha release mediate carcinogen-induced compensatory proliferation and liver tumorigenesis
    Toshiharu Sakurai
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    Cancer Cell 14:156-65. 2008
    ..IL-1 alpha release by necrotic hepatocytes is therefore an important mediator of liver tumorigenesis...
  9. pmc IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer
    Sergei Grivennikov
    Laboratory of Gene Regulation and Signal Transduction, UCSD School of Medicine, University of California San Diego, La Jolla, CA 92093 0723, USA
    Cancer Cell 15:103-13. 2009
    ..Thus, the NF-kappaB-IL-6-Stat3 cascade is an important regulator of the proliferation and survival of tumor-initiating IECs...
  10. pmc I{kappa}B kinase (IKK){beta}, but not IKK{alpha}, is a critical mediator of osteoclast survival and is required for inflammation-induced bone loss
    Maria Grazia Ruocco
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    J Exp Med 201:1677-87. 2005
    ..IKKbeta also protects osteoclasts and their progenitors from tumor necrosis factor alpha-induced apoptosis, and its loss in hematopoietic cells prevents inflammation-induced bone loss...
  11. pmc Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth
    Sergei I Grivennikov
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, California 92093 0723, USA
    Nature 491:254-8. 2012
    ..We propose that barrier deterioration induced by colorectal-cancer-initiating genetic lesions results in adenoma invasion by microbial products that trigger tumour-elicited inflammation, which in turn drives tumour growth...
  12. ncbi request reprint Signaling pathways and genes that inhibit pathogen-induced macrophage apoptosis--CREB and NF-kappaB as key regulators
    Jin Mo Park
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California San Diego, La Jolla, CA 92093, USA
    Immunity 23:319-29. 2005
    ..Here we describe key roles for transcription factor CREB, a target for p38 signaling, and the plasminogen activator 2 (PAI-2) gene, a target for CREB, in maintenance of macrophage survival...
  13. pmc Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis
    Sunhwa Kim
    Department of Pharmacology and Cancer Center, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093 0723, USA
    Nature 457:102-6. 2009
    ..These results explain how advanced cancer cells usurp components of the host innate immune system, including bone-marrow-derived myeloid progenitors, to generate an inflammatory microenvironment hospitable for metastatic growth...
  14. pmc Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression
    Eek Joong Park
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    Cell 140:197-208. 2010
    ..The chronic inflammatory response caused by obesity and enhanced production of IL-6 and TNF may also increase the risk of other cancers...
  15. pmc Loss of acinar cell IKKα triggers spontaneous pancreatitis in mice
    Ning Li
    Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, UCSD, La Jolla, California 92093 0723, USA
    J Clin Invest 123:2231-43. 2013
    ....
  16. pmc Hepatocyte IKKbeta/NF-kappaB inhibits tumor promotion and progression by preventing oxidative stress-driven STAT3 activation
    Guobin He
    Laboratory of Gene Regulation and Signal Transduction, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    Cancer Cell 17:286-97. 2010
    ..Hepatocyte-specific STAT3 ablation prevented HCC development. The negative crosstalk between NF-kappaB and STAT3, which is also evident in human HCC, is a critical regulator of liver cancer development and progression...
  17. pmc Design and characterization of a potent and selective dual ATP- and substrate-competitive subnanomolar bidentate c-Jun N-terminal kinase (JNK) inhibitor
    John L Stebbins
    Infectious and Inflammatory Disease Center, Cancer Center, Sanford Burnham Medical Research Institute, La Jolla, California 92037, USA
    J Med Chem 54:6206-14. 2011
    ..Finally, compound 19 successfully inhibits JNK in a variety of cell-based experiments, as well as in vivo where it is shown to protect against Jo-2 induced liver damage and improve glucose tolerance in diabetic mice...
  18. ncbi request reprint Nod2 mutation in Crohn's disease potentiates NF-kappaB activity and IL-1beta processing
    Shin Maeda
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0723, USA
    Science 307:734-8. 2005
    ..These effects are linked to increased susceptibility to bacterial-induced intestinal inflammation and identify NOD2 as a positive regulator of NF-kappaB activation and IL-1beta secretion...
  19. pmc Constitutive intestinal NF-κB does not trigger destructive inflammation unless accompanied by MAPK activation
    Monica Guma
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    J Exp Med 208:1889-900. 2011
    ..Inflammation is driven by massive TNF production, which requires additional activation of p38 and extracellular-signal-regulated kinase mitogen-activated protein kinases (MAPKs)...
  20. ncbi request reprint Alternative and classical NF-kappa B signaling retain autoreactive B cells in the splenic marginal zone and result in lupus-like disease
    Thomas Enzler
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
    Immunity 25:403-15. 2006
    ..Thus, both classical and alternative NF-kappaB signaling are important for development of lupus-like disease associated with BAFF overproduction. The same mechanisms may be involved in the pathogenesis of human SLE...
  21. pmc Loss of hepatic NF-kappa B activity enhances chemical hepatocarcinogenesis through sustained c-Jun N-terminal kinase 1 activation
    Toshiharu Sakurai
    Laboratory of Gene Regulation and Signal Transduction, School of Medicine, University of California at San Diego, 9500 Gilman Drive MC 0723, La Jolla, CA 92093 0723, USA
    Proc Natl Acad Sci U S A 103:10544-51. 2006
    ....
  22. pmc Targeted deletion of hepatocyte Ikkbeta confers growth advantages
    Katherine S Koch
    Hepatocyte Growth Control and Stem Cell Laboratory, School of Medicine, University of California at San Diego, 9500 Gilman Drive MC 0636, La Jolla, CA 92093 0636, USA
    Biochem Biophys Res Commun 380:349-54. 2009
    ..Increased HCC development in Ikkbeta(Delta hep) mice may also be caused by growth advantages of surviving Ikkbeta-deleted hepatocytes...
  23. ncbi request reprint Kinase MEKK1 is required for CD40-dependent activation of the kinases Jnk and p38, germinal center formation, B cell proliferation and antibody production
    Ewen Gallagher
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, California 92093 0723, USA
    Nat Immunol 8:57-63. 2007
    ..Our data emphasize that MEKK1 is an essential component of signaling cascades needed for thymus-dependent antigen-induced B cell proliferation and antibody production...
  24. pmc Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies
    Jun Hee Lee
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego UCSD, La Jolla, CA 92093 0723, USA
    Science 327:1223-8. 2010
    ....
  25. pmc Saturated fatty acids inhibit induction of insulin gene transcription by JNK-mediated phosphorylation of insulin-receptor substrates
    Giovanni Solinas
    Laboratory of Gene Regulation and Signal Transduction, School of Medicine, University of California at San Diego, 9500 Gilman Drive, MC 0723, La Jolla, CA 92093 0723, USA
    Proc Natl Acad Sci U S A 103:16454-9. 2006
    ..This mechanism may account for the induction of central insulin resistance by free fatty acids...
  26. ncbi request reprint IKKbeta is required for prevention of apoptosis mediated by cell-bound but not by circulating TNFalpha
    Shin Maeda
    Laboratory of Gene Regulation and Signal Transduction, University of California, San Diego, 9500 Gilman Drive, 92093, La Jolla, CA, USA
    Immunity 19:725-37. 2003
    ..Thus, the antiapoptotic function of IKKbeta, which is most critical in situations that involve cell-bound TNFalpha, is mediated partially through attenuation of JNK activity...
  27. pmc Opposing functions of IKKbeta during acute and chronic intestinal inflammation
    Lars Eckmann
    Department of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 105:15058-63. 2008
    ..Our findings caution against the therapeutic use of IKKbeta/NF-kappaB inhibitors in acute inflammatory settings dominated by cell loss and ulceration...
  28. pmc A NOD2-NALP1 complex mediates caspase-1-dependent IL-1beta secretion in response to Bacillus anthracis infection and muramyl dipeptide
    Li Chung Hsu
    Departments of Pharmacology and Pathology, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 105:7803-8. 2008
    ..Thus, NOD2 plays a key role in the B. anthracis-induced inflammatory response by being a critical mediator of IL-1beta secretion...
  29. pmc Genetic and pharmacological inhibition of JNK ameliorates hypoxia-induced retinopathy through interference with VEGF expression
    Monica Guma
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0723, USA
    Proc Natl Acad Sci U S A 106:8760-5. 2009
    ..These results strongly suggest that JNK1 plays a key role in retinal neoangiogenesis and that it represents a new pharmacological target for treatment of diseases where excessive neoangiogenesis is the underlying pathology...
  30. doi request reprint Chronic lymphocytic leukemia of Emu-TCL1 transgenic mice undergoes rapid cell turnover that can be offset by extrinsic CD257 to accelerate disease progression
    Thomas Enzler
    Moores Cancer Center, Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA, USA
    Blood 114:4469-76. 2009
    ....
  31. pmc Dangerous liaisons: STAT3 and NF-kappaB collaboration and crosstalk in cancer
    Sergei I Grivennikov
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA
    Cytokine Growth Factor Rev 21:11-9. 2010
    ..In addition to explaining the molecular pathogenesis of cancer, these interactions also offer opportunities for the design of new therapeutic interventions...
  32. doi request reprint Anthrax toxin induces macrophage death by p38 MAPK inhibition but leads to inflammasome activation via ATP leakage
    Syed Raza Ali
    Laboratory of Signal Transduction, Department of Pharmacology, University of California, San Diego, La Jolla, California, USA
    Immunity 35:34-44. 2011
    ..Prevention of cell death or ATP release through constitutive p38 or AKT activation interfered with inflammasome activation and IL-1β production, thereby compromising antimicrobial immunity...
  33. ncbi request reprint Epithelial cell I kappa B-kinase beta has an important protective role in Clostridium difficile toxin A-induced mucosal injury
    Sungwon Chae
    Department of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    J Immunol 177:1214-20. 2006
    ..difficile toxin A exposure that is mediated, at least in part, through promoting epithelial cell survival by abrogating epithelial cell apoptosis...
  34. pmc Anthrolysin O and other gram-positive cytolysins are toll-like receptor 4 agonists
    Jin Mo Park
    Laboratory of Gene Regulation and Signal Transduction, Dept of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Dr, La Jolla, CA 92093, USA
    J Exp Med 200:1647-55. 2004
    ..We also provide genetic evidence that ALO is required for induction of macrophage apoptosis in response to infection with live B. anthracis and that other CDC family members share the ability to activate TLR4...
  35. pmc Allergen-induced peribronchial fibrosis and mucus production mediated by IkappaB kinase beta-dependent genes in airway epithelium
    David H Broide
    Department of Medicine, Laboratory of Gene Regulation and Signal Transduction, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 102:17723-8. 2005
    ..Overall, these studies show an important role for NF-kappaB regulated genes in airway epithelium in allergen-induced airway remodeling, including peribronchial fibrosis and mucus production...
  36. pmc IKKalpha, a critical regulator of epidermal differentiation and a suppressor of skin cancer
    Pascal Descargues
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, Cancer Center, School of Medicine, University of California, San Diego, La Jolla, CA 92093 0723, USA
    EMBO J 27:2639-47. 2008
    ..Although these are not the only functions of nuclear IKKalpha, this multifunctional protein is a key regulator of keratinocyte and epidermal differentiation and a critical suppressor of skin cancer...
  37. doi request reprint Inflammation and colon cancer
    Janos Terzic
    Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, La Jolla, California, USA
    Gastroenterology 138:2101-2114.e5. 2010
    ..These mechanisms, as well as new approaches to prevention and therapy, are discussed in this review...
  38. pmc B-cell activating factor and v-Myc myelocytomatosis viral oncogene homolog (c-Myc) influence progression of chronic lymphocytic leukemia
    Weizhou Zhang
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 107:18956-60. 2010
    ....
  39. pmc Activation of IKKalpha target genes depends on recognition of specific kappaB binding sites by RelB:p52 dimers
    Giuseppina Bonizzi
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0636, USA
    EMBO J 23:4202-10. 2004
    ..This site links induction of organogenic chemokines and other important regulatory molecules to activation of the alternative pathway...
  40. pmc Streptolysin O promotes group A Streptococcus immune evasion by accelerated macrophage apoptosis
    Anjuli M Timmer
    Department of Pediatrics, Biomedical Sciences Graduate Program, Laboratory of Signal Transduction, University of California, San Diego, La Jolla, California 92093, USA
    J Biol Chem 284:862-71. 2009
    ..We conclude that accelerated, caspase-dependent macrophage apoptosis induced by the pore-forming cytolysin SLO contributes to GAS immune evasion and virulence...
  41. pmc Fibroblast-specific protein 1 identifies an inflammatory subpopulation of macrophages in the liver
    Christoph H Osterreicher
    Department of Medicine, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 108:308-13. 2011
    ..These findings suggest that FSP1 is a marker of a specific subset of inflammatory macrophages in liver injury, fibrosis, and cancer...
  42. ncbi request reprint Inhibition of NF-kappaB in cancer cells converts inflammation- induced tumor growth mediated by TNFalpha to TRAIL-mediated tumor regression
    Jun Li Luo
    Laboratory of Gene Regulation and Signal Transduction, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Cancer Cell 6:297-305. 2004
    ..The latter response is TNFalpha-independent, but depends on another member of the TNF superfamily, TRAIL, whose receptor is induced in NF-kappaB-deficient cancer cells...
  43. ncbi request reprint IKK-beta links inflammation to obesity-induced insulin resistance
    Melek C Arkan
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
    Nat Med 11:191-8. 2005
    ..We suggest that inhibition of IKK-beta, especially in myeloid cells, may be used to treat insulin resistance...
  44. pmc Activation of the E3 ubiquitin ligase Itch through a phosphorylation-induced conformational change
    Ewen Gallagher
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0723, USA
    Proc Natl Acad Sci U S A 103:1717-22. 2006
    ....
  45. pmc IkappaB kinase alpha kinase activity is required for self-renewal of ErbB2/Her2-transformed mammary tumor-initiating cells
    Yixue Cao
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0723, USA
    Proc Natl Acad Sci U S A 104:15852-7. 2007
    ..IKKalpha may represent a novel and specific target for treatment of ErbB2-positive breast cancer...
  46. pmc A liver full of JNK: signaling in regulation of cell function and disease pathogenesis, and clinical approaches
    Ekihiro Seki
    Department of Medicine, University of California, La Jolla, CA, USA
    Gastroenterology 143:307-20. 2012
    ..We review the functions and pathways of JNK in liver physiology and pathology and discuss findings from preclinical studies with JNK inhibitors...
  47. pmc Saturated fatty acids induce c-Src clustering within membrane subdomains, leading to JNK activation
    Ryan G Holzer
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    Cell 147:173-84. 2011
    ..Consumption of a diabetogenic high-fat diet causes the partitioning and activation of c-Src within detergent insoluble membrane subdomains of murine adipocytes...
  48. ncbi request reprint Jun turnover is controlled through JNK-dependent phosphorylation of the E3 ligase Itch
    Min Gao
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0723, USA
    Science 306:271-5. 2004
    ..This pathway modulates cytokine production by effector T cells...
  49. pmc IKKalpha is a critical coregulator of a Smad4-independent TGFbeta-Smad2/3 signaling pathway that controls keratinocyte differentiation
    Pascal Descargues
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0723, USA
    Proc Natl Acad Sci U S A 105:2487-92. 2008
    ..We suggest that a TGFbeta-Smad2/3-IKKalpha axis is a critical Smad4-independent regulator of keratinocyte proliferation and differentiation...
  50. ncbi request reprint Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases
    Hideaki Kamata
    Laboratory of Gene Regulation and Signal Transduction, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Cell 120:649-61. 2005
    ..Antioxidant treatment also prevents TNFalpha-mediated fulminant liver failure without affecting liver regeneration...
  51. pmc NOD2 contributes to cutaneous defense against Staphylococcus aureus through alpha-toxin-dependent innate immune activation
    Petr Hruz
    Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 106:12873-8. 2009
    ....
  52. doi request reprint A NIK-IKKα module expands ErbB2-induced tumor-initiating cells by stimulating nuclear export of p27/Kip1
    Weizhou Zhang
    Department of Pharmacology, Laboratory of Gene Regulation and Signal Transduction, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0723, USA
    Cancer Cell 23:647-59. 2013
    ....
  53. ncbi request reprint Nuclear cytokine-activated IKKalpha controls prostate cancer metastasis by repressing Maspin
    Jun Li Luo
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Cancer Center, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093 0723, USA
    Nature 446:690-4. 2007
    ..We propose that tumour-infiltrating RANKL-expressing cells lead to nuclear IKKalpha activation and inhibition of Maspin transcription, thereby promoting the metastatic phenotype...
  54. pmc Chronic epithelial NF-κB activation accelerates APC loss and intestinal tumor initiation through iNOS up-regulation
    Helena Shaked
    Department of Pharmacology, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 109:14007-12. 2012
    ..The results suggest that persistent NF-κB activation in IEC may accelerate loss of heterozygocity by enhancing nitrosative DNA damage...
  55. pmc Targeting of TAK1 by the NF-kappa B protein Relish regulates the JNK-mediated immune response in Drosophila
    Jin Mo Park
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, 92093 0636, USA
    Genes Dev 18:584-94. 2004
    ..Because the IKK-NF-kappa B module also negatively regulates JNK activation in mammals, thereby controlling inflammation-induced apoptosis, the regulatory cross-talk between the JNK and NF-kappa B pathways appears to be broadly conserved...
  56. pmc NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha
    Jordi Rius
    Laboratory of Gene Regulation and Signal Transduction, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093 0723, USA
    Nature 453:807-11. 2008
    ..IKK-beta is also essential for HIF-1alpha accumulation in macrophages experiencing a bacterial infection. Hence, IKK-beta is an important physiological contributor to the hypoxic response, linking it to innate immunity and inflammation...
  57. ncbi request reprint The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4
    Li Chung Hsu
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093 0636, USA
    Nature 428:341-5. 2004
    ..The pro-apoptotic actions of PKR are mediated both through inhibition of protein synthesis and activation of interferon response factor 3...
  58. pmc Regulation of late B cell differentiation by intrinsic IKKalpha-dependent signals
    David M Mills
    Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 104:6359-64. 2007
    ..Thus, the NIK-IKKalpha-p52 axis is not as linear and exclusive as previous studies suggest, and IKKalpha possesses critical NF-kappaB-independent functions in B cells...
  59. ncbi request reprint The role of the Ah receptor and p38 in benzo[a]pyrene-7,8-dihydrodiol and benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide-induced apoptosis
    Shujuan Chen
    Laboratory of Environmental Toxicology, Department of Pharmacology, University of California, San Diego, La Jolla, California 92093 0636, USA
    J Biol Chem 278:19526-33. 2003
    ..These results confirm that the Ah receptor plays a critical role in B[a]P-7,8-dihydrodiol-induced apoptosis while p38 MAP kinase links the actions of an electrophilic metabolite like BPDE-2 to the regulation of programmed cell death...
  60. ncbi request reprint Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6
    Hans Hacker
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
    Nature 439:204-7. 2006
    ....
  61. pmc Anthrax lethal factor and edema factor act on conserved targets in Drosophila
    Annabel Guichard
    Section of Cell and Developmental Biology, University of California at San Diego, La Jolla, 92093 0349, USA
    Proc Natl Acad Sci U S A 103:3244-9. 2006
    ....
  62. pmc B-cell-derived lymphotoxin promotes castration-resistant prostate cancer
    Massimo Ammirante
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Cancer Center, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093 0723, USA
    Nature 464:302-5. 2010
    ....
  63. pmc JNK1 controls mast cell degranulation and IL-1{beta} production in inflammatory arthritis
    Monica Guma
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Pathology, Division of Rheumatology, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 107:22122-7. 2010
    ..Hence, JNK1 controls mast cell degranulation and FcγR-triggered IL-1β production, in addition to regulating cytokine and matrix metalloproteinase biosynthesis, and is an attractive therapeutic target in inflammatory arthritis...
  64. pmc IkappaB-kinasebeta-dependent NF-kappaB activation provides radioprotection to the intestinal epithelium
    Laurence J Egan
    Laboratory of Mucosal Immunology, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 101:2452-7. 2004
    ..Selective preactivation of NF-kappaB through IKKbeta in intestinal epithelial cells could provide a therapeutic modality that allows higher doses of radiation to be tolerated during cancer radiotherapy...
  65. ncbi request reprint From death receptor to reactive oxygen species and c-Jun N-terminal protein kinase: the receptor-interacting protein 1 odyssey
    Vladislav Temkin
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, CA, USA
    Immunol Rev 220:8-21. 2007
    ..These molecular mechanisms may be involved in neoplastic, autoimmune, neurodegenerative, inflammatory, and metabolic diseases...
  66. ncbi request reprint IKK beta is required for peripheral B cell survival and proliferation
    Zhi Wei Li
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, Cancer Center, University of California San Diego, La Jolla, CA 92093, USA
    J Immunol 170:4630-7. 2003
    ..Thus, IKKbeta provides a requisite role in B cell activation and maintenance and thus is a key determinant of humoral immunity...
  67. pmc JNK-1 deficiency limits macrophage-mediated antigen-induced arthritis
    Monica Guma
    Department of Medicine, University of California at San Diego, La Jolla, California 92093 0663, USA
    Arthritis Rheum 63:1603-12. 2011
    ..To elucidate the nonredundant roles of JNK-1 and JNK-2 in antigen-induced arthritis (AIA)...