Functional study of SIK3
Date Issued
2011
Date
2011
Author(s)
Tsai, Yu-Chen
Abstract
Salt-inducible kinase 3 (SIK3) is a ubiquitously expressed kinase which belongs to member of AMPK family and SIK sub-family. SIK3 has been reported to regulate energy homeostasis and cell cycle in Drosophila and Human. SIK3 is composed of kinase domain, UBA domain, PKA site and Q-rich C-terminal region. The kinase activity of SIK3 is thought to be regulated by LKB1 and GSK-3β. These two kinases could phosphorylate Thr163 in the activation loop to enhance SIK3 kinase activity. SIK3 shares extensive sequence homology with SIK1 and SIK2 in the ATP-binding pocket and catalytic domain. Similar to SIK2 kinase dead mutant SIK2-K49M, SIK3-K37M or K41M mutant is also kinase dead. Knockdown of SIK3 leads to activation of unfolded protein response (UPR) and impaired ER-associated degradation (ERAD). Overexpression of SIK2 or SIK3 can facilitate ERAD process. In contrast, knockdown of SIK2 or SIK3 lead to inhibition of ERAD. In this study, I investigate the potential roles of SIK2, SIK3 and UBQLN1/2 in regulating ERAD.
Subjects
ERAD
ER stress
Type
thesis
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