gp130-Dependent signalling pathway is not enhanced in gp130 transgenic heart after LIF stimulation.
Activation of gp130 transduces a hypertrophic signal in the heart, but it is not clear whether signalling through gp130 is enhanced when gp130 is overexpressed in vivo. We generated gp130 transgenic mice (TG) and examined the activation of signalling pathways downstream of gp130 in the hearts. The tyrosine phosphorylation of gp130 was enhanced, the phosphorylation of STAT3 and ERK (extracellular signal regulated kinase) 1/2 was increased and induction of the beta-myosin heavy chain (MHC) gene was observed in TG hearts without significant phenotypic changes. Intravenous administration of leukaemia inhibitory factor (LIF) induced tyrosine phosphorylation of STAT3 and ERK 1/2 and expression of c-fos and beta-MHC mRNAs in wild-type littermates' (WT) hearts. However, enhancement of STAT3 and ERK 1/2 phosphorylation or augmented mRNA expressions was not observed in TG hearts after LIF stimulation. Next, STAT-induced STAT inhibitor (SSI) mRNA expression was examined. The expression of SSI-1, SSI-2, and SSI-3 mRNAs was significantly augmented in TG hearts after LIF stimulation. These results indicate that overexpressed gp130 does not always enhance downstream signals in the hearts and suggest that the SSI family plays a role in the regulation of the gp130-dependent signalling pathway in the hearts.
Tone
E
E
Department of Molecular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Kunisada
K
K
Kumanogoh
A
A
Negoro
S
S
Funamoto
M
M
Osugi
T
T
Kishimoto
T
T
Yamauchi-Takihara
K
K
D000367:Age Factors; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015152:Blotting, Northern; D015153:Blotting, Western; D001835:Body Weight; D002352:Carrier Proteins / Q000096:biosynthesis; D002460:Cell Line; D050822:Cytokine Receptor gp130; D004268:DNA-Binding Proteins / Q000378:metabolism; D006131:Growth Inhibitors / Q000378:metabolism / Q000494:pharmacology; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000378:metabolism / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000737:chemistry / Q000378:metabolism; D009929:Organ Size; D010641:Phenotype; D010766:Phosphorylation; D014176:Protein Biosynthesis; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015719:Single-Strand Specific DNA and RNA Endonucleases / Q000378:metabolism; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D019076:Transgenes; D014443:Tyrosine / Q000378:metabolism
D015703:Antigens, CD; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; C494200:Il6st protein, mouse; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D008562:Membrane Glycoproteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; C491590:Socs1 protein, mouse; C491409:Socs2 protein, mouse; C491411:Socs3 protein, mouse; C494087:Stat3 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050822:Cytokine Receptor gp130; D014443:Tyrosine; D020928:Mitogen-Activated Protein Kinases; D015719:Single-Strand Specific DNA and RNA Endonucleases; D018995:Myosin Heavy Chains