期刊
MOLECULAR ENDOCRINOLOGY
卷 25, 期 10, 页码 1773-1785出版社
ENDOCRINE SOC
DOI: 10.1210/me.2011-0082
关键词
-
资金
- National Institute of Health [R01 DK69930, R01 DK080344, 3R01DK080344-01A2S1, AG030979, DK80157, R01 DK76902]
We recently found that the adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain and leucine zipper motif (APPL) 1 is essential for mediating adiponectin signal to induce liver kinase B (LKB)1 cytosloic translocation, an essential step for activation of AMP-activated protein kinase (AMPK) in cells. However, the underlying molecular mechanisms remain unknown. Here, we demonstrate that treating C2C12 myotubes with adiponectin promoted APPL1 interaction with protein phosphatase 2A (PP2A) and protein kinase C zeta (PKC zeta), leading to the activation of PP2A and subsequent dephosphorylation and inactivation of PKC zeta. The adiponectin-induced inactivation of PKC zeta results in dephosphorylation of LKB1 at Ser(307) and its subsequent translocation to the cytosol, where it stimulates AMPK activity. Interestingly, we found that metformin also induces LKB1 cytosolic translocation, but the stimulation is independent of APPL1 and the PP2A-PKC zeta pathway. Together, our study uncovers a new mechanism underlying adiponectin-stimulated AMPK activation in muscle cells and shed light on potential targets for prevention and treatment of insulin resistance and its associated diseases. (Molecular Endocrinology 25: 1773-1785, 2011)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据