title: Differential activation of the extracellular signal-regulated kinase, Jun kinase and Janus kinase-Stat pathways by oncostatin M and basic fibroblast growth factor in AIDS-derived Kaposi's sarcoma cells.
abstract: OBJECTIVE
  To determine the integration of signalling pathways associated with two recognized Kaposi's sarcoma (KS) growth factors, oncostatin M (OSM) and basic fibroblast growth factor (bFGF), in the induction of KS cell proliferation.
  
  
  METHODS
  We used protein kinase assays, protein-DNA interactions and AP-1 luciferase assays to study the extracellular signal-regulated kinase (ERK), Janus kinase (JAK)-Stat and Jun kinase (JNK) pathways in AIDS-derived KS cells during stimulation with OSM and bFGF.
  
  
  RESULTS
  Treatment with OSM-induced activation of receptor-associated JAK and phosphorylation of Stat1 and Stat3. Stat1/Stat3 heterodimers interacted with known gamma-interferon-activated sites like elements such as the sis-inducible element (SIE) in the C-fos promoter. In contrast, ligation of the bFGF receptor induced Stat3 phosphorylation and its association with the bFGF receptor, but failed to induce JAK activity or protein complexes which interact with GAS-like oligonucleotides. OSM also induced the activation of ERK2 by activating the serine/threonine kinases Raf-1 and [mitogenactivated protein kinase (MAPK) ERK kinase (MEK1)]-1, while bFGF failed to activate any of the above components. Both OSM and bFGF activated the JNK pathway, along with the activation of MEKkinase (MEKK)-1. JNK control the transcriptional activation of c-Jun. Because the above pathways exert an effect on the expression or activation of activation protein (AP)-1 components, we confirm that OSM and bFGF induce TPA response element (TRE)-luciferase activity synergistically.
  
  
  CONCLUSIONS
  We demonstrate that OSM and bFGF activate distinct as well as shared signalling cascades in KS cells, which integrate to provide a synergistic AP-1 response by which OSM and bFGF may sustain KS cell growth.
authors.affiliation: Department of Medicine, University of California Los Angles School of Medicine 90024, USA.
authors.forename: M
authors.initials: M
authors.lastname: Faris
authors.forename: B
authors.initials: B
authors.lastname: Ensoli
authors.forename: N
authors.initials: N
authors.lastname: Stahl
authors.forename: G
authors.initials: G
authors.lastname: Yancopoulos
authors.forename: A
authors.initials: A
authors.lastname: Nguyen
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.forename: A E
authors.initials: AE
authors.lastname: Nel
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000201:enzymology / Q000503:physiopathology*; D001483:Base Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D008969:Molecular Sequence Data; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000378:metabolism*; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D012514:Sarcoma, Kaposi / Q000201:enzymology / Q000503:physiopathology*; D015398:Signal Transduction / Q000187:drug effects*; D015534:Trans-Activators / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; D006133:Growth Substances; C508351:OSM protein, human; D010455:Peptides; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D016222:Fibroblast Growth Factor 2; D053683:Oncostatin M; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases