Sam68 and ERKs regulate leptin-induced expression of OB-Rb mRNA in C2C12 myotubes

P. Maroni, L. Citterio, R. Piccoletti, P. Bendinelli

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Acute leptin treatment significantly increases the mRNA of the long isoform of leptin receptor (OB-Rb) in C2C12 myotubes after as little as 30 min, without affecting that of the short isoform (OB-Ra). The Sam68 STAR protein has been implicated in leptin signal transduction as an adaptor molecule useful to recruit other signalling proteins. We found that leptin increased Sam68 tyrosine-phosphorylation so decreasing its poly(U)-binding capacity. RT-PCR analysis of the mRNA bound to immunoprecipitated Sam68 showed that Sam68 associated with OB-Rb but not OB-Ra mRNA in control and leptin-treated C2C12 cells. The siRNA-mediated silencing of Sam68 reduced its levels by 89% and abolished the leptin-mediated increase in OB-Rb mRNA. Leptin activates ERKs which in turn might phosphorylate Sam68 modifying its influence on mRNA. We did not observe any changes in Sam68 Ser/Thr phosphorylation but using the specific MEK1 inhibitor PD-98059 showed that leptin-mediated ERK activation is essential for leptin's effect on OB-Rb mRNA expression. Thus it appears that leptin has a positive short-term effect on the regulation of OB-Rb mRNA in C2C12 cells, involving both Sam68 and ERKs. These results might suggest that leptin signal acutely favours its own sensitivity.

Original languageEnglish
Pages (from-to)26-31
Number of pages6
JournalMolecular and Cellular Endocrinology
Volume309
Issue number1-2
DOIs
Publication statusPublished - Oct 15 2009

Fingerprint

Skeletal Muscle Fibers
Leptin
Messenger RNA
Phosphorylation
Protein Isoforms
RNA Isoforms
Poly U
Leptin Receptors
Signal transduction
Small Interfering RNA
Tyrosine
Signal Transduction
Proteins
Chemical activation
Polymerase Chain Reaction
Molecules

Keywords

  • ERKs
  • Leptin
  • Leptin receptor
  • Sam68

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Molecular Biology

Cite this

Sam68 and ERKs regulate leptin-induced expression of OB-Rb mRNA in C2C12 myotubes. / Maroni, P.; Citterio, L.; Piccoletti, R.; Bendinelli, P.

In: Molecular and Cellular Endocrinology, Vol. 309, No. 1-2, 15.10.2009, p. 26-31.

Research output: Contribution to journalArticle

Maroni, P. ; Citterio, L. ; Piccoletti, R. ; Bendinelli, P. / Sam68 and ERKs regulate leptin-induced expression of OB-Rb mRNA in C2C12 myotubes. In: Molecular and Cellular Endocrinology. 2009 ; Vol. 309, No. 1-2. pp. 26-31.
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