Regulation of the SNARE-interacting protein Munc18c tyrosine phosphorylation in adipocytes by protein-tyrosine phosphatase 1B

Jesse Bakke, Ahmed Bettaieb, Naoto Nagata, Kosuke Matsuo, Fawaz Haj

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: Protein-tyrosine phosphatase 1B (PTP1B) is a physiological regulator of insulin signaling and adiposity and is a drug target for the treatment of obesity and diabetes. The molecular mechanisms underlying PTP1B metabolic actions require additional investigation. Results: Herein, we identify Munc18c as a novel PTP1B substrate in adipocytes and in vivo. We demonstrate nutritional regulation of Munc18c in adipose tissue revealing decreased expression upon high fat feeding. In addition, PTP1B deficiency leads to elevated Munc18c tyrosine phosphorylation and dissociation from syntaxin4. At the molecular level, we identify Munc18c Tyr218/219 and Tyr 521 as key residues that mediate Munc18c interaction with PTP1B. Further, we uncover an essential role of Munc18c total tyrosine phosphorylation in general, and Tyr218/219 and Tyr521 in particular, in regulating its interactions and glucose uptake in adipocytes. Conclusion: In conclusion, our findings identify PTP1B as the first known tyrosine phosphatase for Munc18c and a regulator of its phosphorylation and function in adipocytes.

Original languageEnglish (US)
Article number57
JournalCell Communication and Signaling
Volume11
Issue number1
DOIs
StatePublished - 2013

Fingerprint

Munc18 Proteins
Non-Receptor Type 1 Protein Tyrosine Phosphatase
SNARE Proteins
Phosphorylation
Adipocytes
Tyrosine
Adiposity
Medical problems
Phosphoric Monoester Hydrolases
Adipose Tissue
Obesity
Fats
Insulin
Tissue
Glucose
Substrates

Keywords

  • Adipocytes
  • Glucose
  • Munc18c
  • PTP1B
  • SNARE complex

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Biochemistry
  • Medicine(all)

Cite this

Regulation of the SNARE-interacting protein Munc18c tyrosine phosphorylation in adipocytes by protein-tyrosine phosphatase 1B. / Bakke, Jesse; Bettaieb, Ahmed; Nagata, Naoto; Matsuo, Kosuke; Haj, Fawaz.

In: Cell Communication and Signaling, Vol. 11, No. 1, 57, 2013.

Research output: Contribution to journalArticle

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AU - Matsuo, Kosuke

AU - Haj, Fawaz

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AB - Background: Protein-tyrosine phosphatase 1B (PTP1B) is a physiological regulator of insulin signaling and adiposity and is a drug target for the treatment of obesity and diabetes. The molecular mechanisms underlying PTP1B metabolic actions require additional investigation. Results: Herein, we identify Munc18c as a novel PTP1B substrate in adipocytes and in vivo. We demonstrate nutritional regulation of Munc18c in adipose tissue revealing decreased expression upon high fat feeding. In addition, PTP1B deficiency leads to elevated Munc18c tyrosine phosphorylation and dissociation from syntaxin4. At the molecular level, we identify Munc18c Tyr218/219 and Tyr 521 as key residues that mediate Munc18c interaction with PTP1B. Further, we uncover an essential role of Munc18c total tyrosine phosphorylation in general, and Tyr218/219 and Tyr521 in particular, in regulating its interactions and glucose uptake in adipocytes. Conclusion: In conclusion, our findings identify PTP1B as the first known tyrosine phosphatase for Munc18c and a regulator of its phosphorylation and function in adipocytes.

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