Brain-specific kinases 1 and 2 (BRSK1/2) are AMP-activated protein kinase (AMPK) -related kinases that are highly expressed in the mammalian forebrain. Studies using transgenic animal models have shown the role of these kinases in establishing neuronal polarity. BRSK1 and BRSK2 are activated by phosphorylation of threonine residues in the T-loop activation segment of the kinase domain. In vitro studies have shown that the upstream kinase LKB1 in the AMPK cascade can catalyze this phosphorylation. However, to date, no detailed comparative analysis of the molecular regulation of BRSK1/2 has been performed. Here, we provide evidence that excludes the role of another upstream kinase Ca2+/calmodulin-dependent protein kinase kinase β in the AMPK cascade that activates BRSK1/2.
AMPK -related kinases
AMP-activated protein kinase (AMP-activated proteinkinase, AMPK) is the switch of the body's energy metabolism, and research on AMPK has developed rapidly in recent years. The glycogen-binding domain (GBD) region was found in the β subunit, and the CBS region was found in the gamma subunit, and their functions were studied. The activity of AMPK is regulated by AMP in three different ways in the body. It has been found in mammals that AMPK is regulated by its upstream kinase LKB1, and AMPK's regulation of the body is not only reflected in energy metabolism, but also includes gene expression, protein translation, and cell growth.
Figure 1. Protein structure of AMPK.
Introductions
Brain specific expression protein (BRSK1/2) is an AMPK-related protein kinase that plays an important role in the establishment of nerve cell polarity, the development of synapses and the transmission of neurotransmitters. The N-terminal catalytic domain of BRSKs is accompanied by a long non-catalytic domain at the back end, which is necessary for the correct functioning of the kinase function. However, the regulatory role and mechanism of this region are still quite unclear. Through the study of kinase activity, we first discovered that two sequence conserved regions (SCR1 and SCR2) on the C-terminal domain of BRSK2 have inhibitory effects on kinase activity.
BRSK kinases and cancer
From the perspective of the world, the incidence of gastric cancer is higher, ranking fourth among malignant tumors; throughout China, the incidence and mortality of gastric cancer are higher, ranking second in malignant tumors. The number of deaths from malignant diseases is also the highest among malignant tumors of the digestive system. Radical surgery is currently the only possible cure for early gastric cancer, but because the early symptoms of gastric cancer are not typical, patients often have no obvious specific symptoms. In addition, the popularity of screening for gastric cancer in China is not high. At that time, the disease was in the middle and late stages, and the opportunity for radical surgery was lost. Surgical treatment combined with radiotherapy and chemotherapy have made some progress in the treatment of advanced gastric cancer, but the prognosis and quality of life of patients are still not ideal and need to be improved. Therefore, further strengthening the research on the mechanism of gastric cancer occurrence and development, and looking for biomarkers with greater sensitivity and specificity, will help early detection and intervention of tumors, predict the prognosis of tumors, and develop more effective anti-tumor drugs. Important content in the prevention and treatment of gastric cancer. Brain-selective protein kinase-2 (BRSK2) is a member of the AMP-activated protein kinase / AMPK family. Early research focused on its function with the nervous system. As the research continues, it has been found that BRSK2 can affect cell proliferation and apoptosis by regulating the cell cycle, and plays an important role in the occurrence and progression of tumors such as pancreatic cancer. Studies have shown that BRSK2 is also expressed in gastric cancer.
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