RGD Reference Report - Hypertrophic responses to cardiotrophin-1 are not mediated by STAT3, but via a MEK5-ERK5 pathway in cultured cardiomyocytes. - Rat Genome Database

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Hypertrophic responses to cardiotrophin-1 are not mediated by STAT3, but via a MEK5-ERK5 pathway in cultured cardiomyocytes.

Authors: Takahashi, N  Saito, Y  Kuwahara, K  Harada, M  Tanimoto, K  Nakagawa, Y  Kawakami, R  Nakanishi, M  Yasuno, S  Usami, S  Yoshimura, A  Nakao, K 
Citation: Takahashi N, etal., J Mol Cell Cardiol. 2005 Jan;38(1):185-92. Epub 2004 Dec 10.
RGD ID: 1582264
Pubmed: PMID:15623435   (View Abstract at PubMed)
DOI: DOI:10.1016/j.yjmcc.2004.10.016   (Journal Full-text)

gp130-dependent signaling is known to play a critical role in the onset of heart failure. In that regard, cardiotrophin-1 (CT-1) activates several signaling pathways via gp130, and induces hypertrophy in neonatal rat cardiomyocytes. Among the mediators activated by CT-1, STAT3 is thought to be important for induction of cell hypertrophy, though its precise function in the CT-1 signaling pathway is not fully understood. In the present study, therefore, to better understand the significance of STAT3 activity in CT-1 signaling, we infected cultured cardiomyocytes with adenoviral vectors harboring a dominant-negative STAT3 mutant or one of two endogenous negative regulators of cytokine signaling via the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways [suppressor of cytokine signaling (SOCS) 1 and 3] and then examined their effects on three indexes of CT-1-induced cell hypertrophy: protein synthesis, secretion of brain natriuretic peptide and changes in cell surface area. In control cells, CT-1-induced both STAT3 phosphorylation and cell hypertrophy. Overexpression of dominant-negative STAT3 mutant suppressed CT-1-induced STAT3 phosphorylation, but did not affect cell hypertrophy. On the other hand overexpression of SOCS1 or SOCS3 inhibited both CT-1-induced STAT3 phosphorylation and cell hypertrophy. CT-1 also induced phosphorylations of ERK1/2 and ERK5 in cardiomyocytes, and those, too, were suppressed by overexpression of SOCSs. CT-1-induced cell hypertrophy was suppressed by overexpression of a dominant-negative MEK5 mutant, and not by overexpression of a dominant-negative MEK1 mutant. These findings indicate that the major pathway responsible for the hypertrophic responses to CT-1 is not JAK-STAT3 pathway nor MEK1-ERK1/2 pathway, but MEK5-ERK5 pathway.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ctf1Ratleukemia inhibitory factor signaling pathway  IMP  RGD 
Map2k5Ratpositive regulation of cell growth  IMP  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ctf1Ratcytokine activity  IMP  RGD 
Ctf1Ratleukemia inhibitory factor receptor binding  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ctf1  (cardiotrophin 1)
Map2k5  (mitogen activated protein kinase kinase 5)


Additional Information