Role of extracellular signal-regulated kinase 5 in adipocyte signaling

Hong Zhu, Sara Guariglia, Wenjing Li, Deborah Brancho, Zhao V. Wang, Philipp E. Scherer, Chi Wing Chow

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Increased adiposity due to energy imbalance is a critical factor of the epidemic crisis of obesity and type II diabetes. In addition to the obvious role in energy storage, regulatory factors are secreted from adipose depots to control appetite and cellular homeostasis. Complex signaling cross-talks within adipocyte are also evident due to the metabolic and immune nature of adipose depots. Here, we uncover a role of extracellular signal-regulated kinase 5 (ERK5) in adipocyte signaling. We find that deletion of ERK5 in adipose depots (adipo-ERK5-/-) increases adiposity, in part, due to increased food intake. Dysregulated secretion of adipokines, leptin resistance, and impaired glucose handling are also found in adipo-ERK5-/- mice. Mechanistically, we show that ERK5 impinges on transcription factor NFATc4. Decreased phosphorylation at the conserved gatekeeping Ser residues and increased nuclear localization of NFATc4 are found in adipo-ERK5-/- mice. We also find attenuated PKA activation in adipo-ERK5-/- mice. In response to stimulation of β-adrenergic G-protein-coupled receptor, we find decreased NFATc4 phosphorylation and impaired PKA activation in adipo-ERK5-/- mice. Reduced cAMP accumulation and increased phosphodiesterase activity are also found. Together, these results demonstrate integration of ERK5 with NFATc4 nucleo-cytoplasmic shuttling and PKA activation in adipocyte signaling.

Original languageEnglish (US)
Pages (from-to)6311-6322
Number of pages12
JournalJournal of Biological Chemistry
Volume289
Issue number9
DOIs
StatePublished - Feb 28 2014

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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