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A complete map of the Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) signaling pathway
Journal of Cell Communication and Signaling ( IF 4.1 ) Pub Date : 2020-11-02 , DOI: 10.1007/s12079-020-00592-1
Mohd Altaf Najar 1 , D A B Rex 1 , Prashant Kumar Modi 1 , Nupur Agarwal 1 , Shobha Dagamajalu 1 , Gayathree Karthikkeyan 1 , Manavalan Vijayakumar 2 , Aditi Chatterjee 1, 3 , Uma Sankar 4 , T S Keshava Prasad 1
Affiliation  

Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) is a serine/threonine-protein kinase belonging to the Ca2+/calmodulin-dependent protein kinase subfamily. CAMKK2 has an autocatalytic site, which gets exposed when Ca2+/calmodulin (CAM) binds to it. This results in autophosphorylation and complete activation of CAMKK2. The three major known downstream targets of CAMKK2 are 5′-adenosine monophosphate (AMP)-activated protein kinase (AMPKα), calcium/calmodulin-dependent protein kinase 1 (CAMK1) and calcium/calmodulin-dependent protein kinase 4 (CAMK4). Activation of these targets by CAMKK2 is important for the maintenance of different cellular and physiological processes within the cell. CAMKK2 is found to be important in neuronal development, bone remodeling, adipogenesis, and systemic glucose homeostasis, osteoclastgensis and postnatal myogensis. CAMKK2 is reported to be involved in pathologies like Duchenne muscular dystrophy, inflammation, osteoporosis and bone remodeling and is also reported to be overexpressed in prostate cancer, hepatic cancer, ovarian and gastric cancer. CAMKK2 is involved in increased cell proliferation and migration through CAMKK2/AMPK pathway in prostate cancer and activation of AKT in ovarian cancer. Although CAMKK2 is a molecule of great importance, a public resource of the CAMKK2 signaling pathway is currently lacking. Therefore, we carried out detailed data mining and documentation of the signaling events associated with CAMKK2 from published literature and developed an integrated reaction map of CAMKK2 signaling. This resulted in the cataloging of 285 reactions belonging to the CAMKK2 signaling pathway, which includes 33 protein–protein interactions, 74 post-translational modifications, 7 protein translocation events, and 22 activation/inhibition events. Besides, 124 gene regulation events and 25 activator/inhibitors involved in CAMKK2 activation were also cataloged. The CAMKK2 signaling pathway map data is made freely accessible through WikiPathway database (https://www.wikipathways.org/index.php/Pathway:WP4874). We expect that data on a signaling map of CAMKK2 will provide the scientific community with an improved platform to facilitate further molecular as well as biomedical investigations on CAMKK2 and its utility in the development of biomarkers and therapeutic targets.



中文翻译:

钙/钙调蛋白依赖性蛋白激酶激酶 2 (CAMKK2) 信号通路的完整图谱

钙/钙调蛋白依赖性蛋白激酶激酶 2 (CAMKK2) 是一种丝氨酸/苏氨酸蛋白激酶,属于 Ca 2+ /钙调蛋白依赖性蛋白激酶亚家族。CAMKK2 有一个自催化位点,当 Ca 2+/钙调蛋白(CAM)与其结合。这导致 CAMKK2 的自磷酸化和完全激活。CAMKK2 的三个主要已知下游靶标是 5'-磷酸腺苷 (AMP) 活化蛋白激酶 (AMPKα)、钙/钙调蛋白依赖性蛋白激酶 1 (CAMK1) 和钙/钙调蛋白依赖性蛋白激酶 4 (CAMK4)。CAMKK2 激活这些目标对于维持细胞内不同的细胞和生理过程很重要。发现 CAMKK2 在神经元发育、骨重塑、脂肪生成和全身葡萄糖稳态、破骨细胞生成和出生后肌生成中很重要。据报道,CAMKK2 与杜氏肌营养不良症、炎症、骨质疏松症和骨重塑等病理有关,并且据报道在前列腺癌、肝癌、卵巢癌和胃癌。CAMKK2 在前列腺癌中通过 CAMKK2/AMPK 通路参与增加的细胞增殖和迁移以及在卵巢癌中激活 AKT。尽管CAMKK2是一个非常重要的分子,但目前缺乏CAMKK2信号通路的公共资源。因此,我们从已发表的文献中对与 CAMKK2 相关的信号事件进行了详细的数据挖掘和记录,并开发了 CAMKK2 信号的综合反应图。这导致对属于 CAMKK2 信号通路的 285 个反应进行编目,其中包括 33 个蛋白质-蛋白质相互作用、74 个翻译后修饰、7 个蛋白质易位事件和 22 个激活/抑制事件。除了,124 个基因调控事件和 25 个参与 CAMKK2 激活的激活剂/抑制剂也被编目。CAMKK2 信号通路图数据可通过 WikiPathway 数据库 (https://www.wikipathways.org/index.php/Pathway:WP4874) 免费访问。我们预计 CAMKK2 信号图谱上的数据将为科学界提供一个改进的平台,以促进对 CAMKK2 的进一步分子和生物医学研究及其在生物标志物和治疗靶点开发中的效用。

更新日期:2020-11-02
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