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
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
leukemia inhibitory factor signaling pathway  IMP 1582264 RGD 
positive regulation of cell growth  IMP 1582264 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cytokine activity  IMP 1582264 RGD 
leukemia inhibitory factor receptor binding  IMP 1582264 RGD 

Objects Annotated

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


Additional Information