AMP-activated protein kinase (AMPK) is a key regulator of cellular and systemic energy homeostasis. Recently, 12 AMPK-related kinases (BRSK1, BRSK2, NUAK1, NUAK2, QIK, QSK, SIK, MARK1, MARK2, MARK3, MARK4, and MELK) have been identified, which are closely related to the AMPK catalytic domain through sequence Related. The protein kinase LKB1 acts as an upstream upstream kinase that activates AMPK and 11 AMPK-related kinases by activating phosphorylation of conserved threonine residues in its T-loop region. Further sequence analysis has identified the eight-membered SNRK kinase family as a distant relative of AMPK. Qik belongs to the AMPK/SNF1 kinase family. It is a ubiquitously expressed protein and is up-regulated by the hormone-regulated form Qin Hou soon afterwards. In vitro kinase tests indicate that Qik is capable of autophosphorylation.
Inrroductions
Qik belongs to the AMPK/SNF1 family of serine threonine kinases. These proteins show homology in the catalytic domain and correlation in a domain called the SNF1 homology region. The latter defines the AMPK/SNF1 kinase family. Members of this family differ in non-catalytic sequences, which may determine biological function and confer substrate specificity. The prototype of this family is AMP-activated kinase (AMPK) and its yeast homolog SNF1. These kinases are conserved in fungi, plants and animals. They are upregulated by AMP in response to ATP consumption. They promoted the activation of the ATP anabolic pathway and the down-regulation of the ATP consumption anabolic pathway. AMPK/SNF1 kinase is stress-induced. They are also called battery fuel gauges. Important member of the AMPK/SNF1 family.
Locations
QIK (Qin-induced kinase) is a universally expressed protein with the highest mRNA levels detected in adipose tissue. QIK phosphorylates the human adaptor insulin receptor substrate 1 at S794 (same as AMPK Residues), suggesting that SIK2 may mediate insulin signaling. QIK also inhibits CREB-mediated gene expression by phosphorylating CREB's coactivator TORC2 at the same site as AMPK. TORC2 phosphorylation results in interaction with 14-3-3, sequestering TORC2 into the cytoplasm and preventing CREB-mediated transcription. In addition, in mice lacking LKB1 expression in the liver, TORC2 was not phosphorylated at the AMPK/QIK site and was located in the nucleus.
Functions
QIK exerts a variety of physiological functions mainly through phosphorylation of its downstream substrate and regulation of its activity. QIK can regulate the efficiency of insulin signal transduction and cause insulin resistance in diabetic animals through phosphorylation of the Ser794 site of IRS1; the co-activator of CREB TORC2 is phosphorylated by QIK to form a dimer with 1433 protein and stays in cells In the slurry. Smad3 is an important molecule of the TGFβ signaling pathway. Bioinformatics analysis revealed that the Thr56 and Thr132 sites of the Smad3 protein sequence conform to the conserved amino acid sequence characteristics of the phosphorylated substrate of QIK, suggesting that Smad3 is likely to be the new role of QIK Things. Whether SIK2 regulates the TGF (signaling pathway through regulating Smad3 phosphorylation is the focus of our next research. SIK2 positively regulates TGFβ signaling pathway may have important physiological significance. Existing studies have shown that SIK2 plays an important role in regulating adipocytes and insulin signaling pathways, but no further functional studies have been reported on SIK2. The TGFβ signaling pathway is composed of ligands, receptors, and members of the SMADs family that transduce signals. Among them, the ligand refers to the TGFβ superfamily and consists of TGFβs, activins, and bone morphogenetic proteins. The development and renewal processes of tissues play an important regulatory role. Because the TGFβ signaling pathway mainly performs the function of growth inhibition, inactivation of this pathway will cause tumor cells to be less sensitive to the TGFβ growth inhibitory function. As a molecule that positively regulates the TGFβ signaling pathway, SIK2 is likely to be involved in cell growth and proliferation. Recent studies have reported that SIK2 can negatively regulate insulin-induced cell survival pathways and promote hyperglycemia-induced glial cell death, but the mechanism is not very clear. SIK2 positively regulates the TGFβ signaling pathway and is likely to play an important role in this process.
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