Molecular mechanism of SH2B1 in regulating JAK2/IRS2 during obesity development
10.3969/j.issn.1672-7347.2010.03.004
- VernacularTitle:SH2B1调控JAK2/IRS2在肥胖症发病中的分子机制
- Author:
Chaojun DUAN
;
Cane TANG
;
Lan LIAO
;
Cui LI
;
Tao SU
;
Zhuchu CHEN
- Publication Type:Journal Article
- Keywords:
SH2B1;
obesity;
insulin receptor substrate-2;
leptin signal pathway
- From:
Journal of Central South University(Medical Sciences)
2010;35(3):209-214
- CountryChina
- Language:Chinese
-
Abstract:
Objective In order to investigate the effect of SH2B1 on leptin signal transduction JAK2/IRS2 and its biological function.Methods Vitro kinase assay and Western blot were used to analyse tyrosine phosphorylatin of key molecule JAK2 and insulin receptor substrate-2 (IRS2). ELISA was used to measure the plasma leptin levels in mice. The postnatal growth of mice was monitored over 27 weeks. Results SH2B1 dramatically enhanced the leptin-stimulated tyrosine phosphorylation of JAK2 and IRS2 in HEK293 cells stably expressing LRb (HEK239~(LRb)). Leptin-stimulated activation of hypothalamic JAK2 and phosphorylation of hyphothalamic IRS2 were significantly impaired in SH2B1~(-/-) mice. The deletion of SH2B1 led to leptin resistance,and fasting and randomly fed plasma leptin levels were respectively 3.2 times and 5.1 times higher in SH2B1~(-/-) males than wild-type littermates at 15 weeks of age. SH2B1~(-/-) males gained body weight rapidly and exceeded wild-type littermates from 5~(th) week. SH2B1(-/-) (at 21 weeks) was approximately twice heavier than wild-type littermates.Conclusion SH2B1 is an endogenous enhancer of leptin sensitivity and required for maintaining normal bodyweight in mice via leptin JAK2/IRS2 pathway.
