PMID- 33136287 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20211130 IS - 1873-9601 (Print) IS - 1873-961X (Electronic) IS - 1873-9601 (Linking) VI - 15 IP - 2 DP - 2021 Jun TI - A complete map of the Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) signaling pathway. PG - 283-290 LID - 10.1007/s12079-020-00592-1 [doi] AB - Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) is a serine/threonine-protein kinase belonging to the Ca(2+)/calmodulin-dependent protein kinase subfamily. CAMKK2 has an autocatalytic site, which gets exposed when Ca(2+)/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 (AMPKalpha), 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. FAU - Najar, Mohd Altaf AU - Najar MA AUID- ORCID: 0000-0002-3044-3772 AD - Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, 575018, India. FAU - Rex, D A B AU - Rex DAB AUID- ORCID: 0000-0002-9556-3150 AD - Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, 575018, India. FAU - Modi, Prashant Kumar AU - Modi PK AD - Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, 575018, India. FAU - Agarwal, Nupur AU - Agarwal N AUID- ORCID: 0000-0002-1447-2397 AD - Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, 575018, India. FAU - Dagamajalu, Shobha AU - Dagamajalu S AUID- ORCID: 0000-0002-0899-2839 AD - Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, 575018, India. FAU - Karthikkeyan, Gayathree AU - Karthikkeyan G AUID- ORCID: 0000-0002-5965-2957 AD - Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, 575018, India. FAU - Vijayakumar, Manavalan AU - Vijayakumar M AD - Department of Surgical Oncology, Yenepoya Medical College and Hospital, Yenepoya (Deemed to be University), Mangalore, 575018, India. FAU - Chatterjee, Aditi AU - Chatterjee A AUID- ORCID: 0000-0001-8474-5824 AD - Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, 575018, India. AD - Institute of Bioinformatics, International Technology Park, Bangalore, Karnataka, 560066, India. FAU - Sankar, Uma AU - Sankar U AD - Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, 635 Barnhill Drive, MS-5055, Indianapolis, IN, 46202, USA. FAU - Prasad, T S Keshava AU - Prasad TSK AUID- ORCID: 0000-0002-6206-2384 AD - Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, 575018, India. keshav@yenepoya.edu.in. LA - eng GR - R01 AR068332/AR/NIAMS NIH HHS/United States GR - R01 AR076477/AR/NIAMS NIH HHS/United States PT - Journal Article DEP - 20201102 PL - Netherlands TA - J Cell Commun Signal JT - Journal of cell communication and signaling JID - 101308338 PMC - PMC7990983 OTO - NOTNLM OT - Adenocarcinoma OT - CAMKK2 OT - Calcium signaling pathway OT - Molecular association OT - Signaling module OT - Tumorigenesis COIS- The authors report no conflict of interest. EDAT- 2020/11/03 06:00 MHDA- 2020/11/03 06:01 PMCR- 2021/06/01 CRDT- 2020/11/02 12:12 PHST- 2020/10/12 00:00 [received] PHST- 2020/10/19 00:00 [accepted] PHST- 2020/11/03 06:00 [pubmed] PHST- 2020/11/03 06:01 [medline] PHST- 2020/11/02 12:12 [entrez] PHST- 2021/06/01 00:00 [pmc-release] AID - 10.1007/s12079-020-00592-1 [pii] AID - 592 [pii] AID - 10.1007/s12079-020-00592-1 [doi] PST - ppublish SO - J Cell Commun Signal. 2021 Jun;15(2):283-290. doi: 10.1007/s12079-020-00592-1. Epub 2020 Nov 2.