In:
Cell Communication and Signaling, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2013-12)
Abstract:
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 Tyr 218/219 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 Tyr 218/219 and Tyr 521 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.
Type of Medium:
Online Resource
ISSN:
1478-811X
DOI:
10.1186/1478-811X-11-57
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2013
detail.hit.zdb_id:
2126315-2
SSG:
12
