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Last update 08 May 2025

CAMKK1

Last update 08 May 2025

Basic Info

Synonyms

calcium/calmodulin dependent protein kinase kinase 1, Calcium/calmodulin-dependent protein kinase kinase 1, calcium/calmodulin-dependent protein kinase kinase 1, alpha

+ [12]

Introduction

Calcium/calmodulin-dependent protein kinase that belongs to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Phosphorylates CAMK1, CAMK1D, CAMK1G and CAMK4. Involved in regulating cell apoptosis. Promotes cell survival by phosphorylating AKT1/PKB that inhibits pro-apoptotic BAD/Bcl2-antagonist of cell death.

Drugs associated with CAMKK1

STO-609

Target

CAMKK1 x CAMKK2

Mechanism

CAMKK1 inhibitors [+1]

Active Org.

Eyedesis Biosciences LLC [+1]

Originator Org.

Duke University School of Medicine

Active Indication

Graft vs Host Disease [+1]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CAMKK1

100 Translational Medicine associated with CAMKK1

0 Patents (Medical) associated with CAMKK1

126

Literatures (Medical) associated with CAMKK1

01 Apr 2025·Fish Physiology and Biochemistry

Carbonate alkalinity induces stress responses and renal and metabolic disorders in Nile tilapia: mitigation by camel whey protein hydrolysate diet

Article

Author: Metwally, Mohamed M M ; Osman, Ali ; Khamis, Tarek ; Mohamed, Amany Abdel-Rahman ; Ibrahim, Rowida E ; Younis, Elsayed M ; Abdelwarith, Abdelwahab A ; Davies, Simon J ; Abd-Elhakim, Yasmina M

Alkaline stress is a major concern in aquaculture that badly affects the aquatic species' health and hemostasis. This research investigated the effect of carbonate alkalinity exposure on the gills and kidney organs as important organs for hemostasis, as well as the ameliorative role of camel protein hydrolysates (CPH) as dietary additives against alkaline stress detrimental impacts in Nile tilapia (Oreochromis niloticus). The fish (n = 160) were divided into four groups (G1, G2, G3, and G4), with the control (G1) fed a basal diet, while G2 was fed a basal diet supplemented with 75 g CPH/kg and was reared in freshwater (carbonate alkalinity of 1.4 µmol/L, pH = 7.19). The G3 and G4 were reared in alkaline water (carbonate alkalinity of 23.8 µmol/L, pH = 8.65) and fed the same diets as G1 and G2 for 30 days, respectively. The fish were stocked under a water temperature of 26.4 ± 1.5 °C, and the diets were introduced to the fish three times daily at a rate of 4% of their body weight. The results of this research showed that alkaline exposure increased kidney function parameters (creatinine, urea, and uric acid), glucose, and cortisol levels in the exposed fish. Alkaline exposure reduced the blood electrolytes level (calcium, magnesium, sodium, potassium, and chloride) and branchial antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and reduced glutathione) and elevated malondialdehyde level in the exposed fish. Significant downregulation of the branchial expression of Na⁺/K⁺ ATPase α-3 subunit (0.17-fold), calcium/calmodulin-dependant protein kinase 1 β (0.23 fold), chloride channel protein 2 (0.38-fold), solute carrier family 12 a 2 (0.33-fold), and solute carrier family 4 a 4 (0.21-fold) was in the fish-reared under carbonate alkalinity stress. Alkaline exposure induced severe histopathological changes in the gills and kidney tissue architecture including inflammatory, circulatory, degenerative, and progressive responses. Supplementation of the Nile tilapia diet with 75 g CPH/kg ameliorated renal function and balanced the blood electrolytes, glucose, and cortisol levels in the alkaline-exposed fish. Modulation of the branchial gene expression profile and improving the gills and kidney microstructure were consequences of feeding on CPH diets during alkaline stress situations. Overall, fortifying the Nile tilapia diets with 75 g CPH/kg helps the fish restore their hemostasis and metabolic status during alkaline stress exposure which enables the sustainable culture of this species in such conditions.

01 Apr 2025·OMICS: A Journal of Integrative Biology

Orchestrating Intracellular Calcium Signaling Cascades by Phosphosite-Centric Regulatory Network: A Comprehensive Analysis on Kinases CAMKK1 and CAMKK2

Article

Author: Shivamurthy, Prathik Basthikoppa ; Varghese, Susmi ; Ahmed, Mukhtar ; Nisar, Mahammed ; Gopalakrishnan, Athira Perunelly ; Modi, Prashant Kumar ; Raju, Rajesh ; Ummar, Samseera ; Prasad, Thottethodi Subrahmanya Keshava ; Pai, Vinitha Ramanath ; John, Levin ; Mahin, Althaf

Intracellular calcium signaling is a cornerstone in cell biology and a key molecular target for human health and disease. Calcium/calmodulin dependent protein kinase kinases, CAMKK1 and CAMKK2 are serine/threonine kinases that contribute to the regulation of intracellular calcium signals in response to diverse stimuli. CAMKK1 generally has stable dynamics, whereas CAMKK2 dysregulation triggers oncogenicity and neurological disorders. To differentiate the phosphosignaling hierarchy associated with predominant phosphosites of CAMKK1 and CAMKK2, we assembled and analyzed the global cellular phosphoproteome datasets. We found that predominant phosphosites in CAMKK1 and CAMKK2 are located outside the kinase domain, and their phosphomotifs are highly homologous. Further, we employed a coregulation analysis approach to these predominant phosphosites, to infer the co-occurrence patterns of phosphorylations within CAMKKs and the coregulation patterns of other protein phosphosites with CAMKK sites. We report herein that independent phosphorylations at CAMKK2 S100 and S511 increase their enzymatic activity in the presence of calcium/calmodulin. In addition, the study unveils kinase-substrate associations such as RPS6KB1 as a novel high-confidence upstream kinase of both CAMKK1 S74 and CAMKK2 S100. Further, CAMKK2 was identified as a primary orchestrator in mediating intracellular calcium signaling cascades compared to CAMKK1 based on coregulation patterns of phosphosites from proteins involved in the calcium signaling pathway. These molecular details shed promising insights into the pathophysiology of several diseases such as cancers and psychiatric disorders associated with kinase activity dysregulations of CAMKK2 and further open the avenue for novel PTM-directed therapeutic strategies to regulate CAMKK2.

01 Feb 2025·International Journal of Biological Macromolecules

Mechanisms of Nrf2 suppression and Camkk1 upregulation in Echinococcus granulosus-induced bone loss

Article

Author: Dai, Yi ; Wang, Sibo ; Xiao, Jun ; Huang, Yiping ; Huang, Yansheng ; Ma, Yibo ; Sun, Haohao ; Liu, Yaqing ; Ren, Qian

Osteoclast differentiation is essential for maintaining bone metabolism, and its dysregulation, particularly in the context of Echinococcus granulosus (CE) infection, can lead to severe bone loss. This study explores a novel mechanism by which CE protoscolices (PSC) drive osteoclast differentiation through the inhibition of Nrf2, followed by the upregulation of Camkk1. Transcriptome sequencing revealed a significant down-regulation of Nrf2 in cells treated with PSC. This was confirmed by Western blot and Q-PCR assays showing reduced Nrf2 protein and gene levels. In vivo studies with Nrf2 knockout mice demonstrated that the absence of Nrf2 exacerbates bone loss induced by PSC in both the spine and lower limbs, as observed through Micro-CT imaging and TRAP staining.Further investigations identified Camkk1 as a key downstream target of Nrf2. Using high-throughput sequencing and CO-IP experiments, we established that Nrf2 directly interacts with and regulates Camkk1. Functional assays indicated that PSC-induced upregulation of Camkk1 is significantly enhanced by Nrf2 knockdown, while silencing Camkk1 alone inhibits osteoclast differentiation.The therapeutic potential of this pathway was evaluated by screening small molecule inhibitors of Camkk1, with Crenolani emerging as a potent compound. In vivo administration of Crenolani in PSC-treated mice significantly alleviated bone loss in a dose-dependent manner.These findings elucidate a crucial molecular mechanism in osteoclast differentiation driven by CE infection and propose a promising therapeutic strategy for combating CE-induced bone destruction. This study advances our understanding of bone.

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CAMKK1

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