Other Name(s): adenosine monophosphate-activated protein kinase, AMPK
Drug Target Analysis Report Drug Target Analysis Report Content

About the Target

AMPK, also known as adenosine monophosphate-activated protein kinase or PRKAA2, plays a crucial role in various cellular processes and signaling pathways. Metformin, a commonly used drug for diabetes, has been found to induce cell death in melanoma cells through both AMPK-dependent and -independent pathways [1]. AMPK activation is mediated by metabolite sensors such as aldolase, Sestrin, CASTOR1, and SAMTOR, which sense and signal the availability of glucose, arginine, leucine, and SAM/methionine, respectively [2]. Activation of AMPK by PMI-5011/KOE has been observed in muscle cells, and it can occur through different mechanisms, including direct binding to the gamma subunit of AMPK, promoting Thr172-phosphorylation of the alpha subunit, or inhibiting Thr172-dephosphorylation [3]. In failing hearts, AMPK activation has been shown to attenuate cardiac hypertrophy and improve oxidative phosphorylation through regulation of glucose transporters, fatty acid uptake, and inhibition of the mTORC1 pathway [4]. Additionally, increased expression of PRKAA2 has been observed in induced sinoatrial bodies, indicating its potential role in pacemaking and AMPK-mediated signaling [5]. These findings highlight the diverse functions and regulatory mechanisms of AMPK in various biological contexts.
Based on the provided context information, here is a comprehensive summary of the AMPK (also known as PRKAA2) signaling pathway:

AMPK is a key regulator of cellular energy status and plays a role in energy homeostasis [8]. It acts as a sensor of cellular energy and coordinates energy reserves with biosynthetic activity by regulating mTORC1 [8].

AMPK activation occurs on the surface of the lysosome and signals a need for catabolic activity while suppressing mTORC1 [8]. This recruitment of AMPK to the lysosomal surface requires the addition of a myristic acid lipid tail [8].

In female magpies, AMPK is upregulated in the AMPK signaling pathway, suggesting a role in mediating dietary restriction [7]. This pathway is involved in energy metabolism and activates glucose and fatty acid uptake and oxidation while inhibiting gluconeogenesis, glycogen synthesis, and protein synthesis [6].

AMPK activation in female magpies may help regulate energy dynamics induced by stress resistance [6]. This is supported by the upregulation of G6Pase, an enzyme involved in gluconeogenesis and glycogenolysis [6].

Male magpies, on the other hand, upregulate genes encoding SIRT1, another enzyme associated with stress resistance and longevity [6]. This indicates that males regulate longevity through SIRT1 and CREB stress resistance genes [6].

AMPK is also implicated in spermatogenesis, where it regulates tight junction (TJ) dynamics, lactate production, and Sertoli cell proliferation [7]. It co-localizes with mTORC1 on the lysosomal surface and suppresses mTORC1 activity [8].

In a melanoma context, enhanced production of phosphatidic acid (PA) by overexpression of PLD leads to aberrant mTOR activation in the absence of LKB1/AMPK regulation [10]. This dysregulation results in increased cell proliferation and growth [10].

In summary, AMPK plays a crucial role in cellular energy homeostasis and is involved in various biological processes such as energy metabolism, stress resistance, longevity, and spermatogenesis. Its dysregulation or aberrant activation can have implications in disease contexts, highlighting the importance of understanding its mechanisms of action.

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Note: If you are interested in the full version of this target analysis report, or if you'd like to learn how our AI-powered BDE-Chem can design therapeutic molecules to interact with the PRKAA2 target at a cost 90% lower than traditional approaches, please feel free to contact us at BD@silexon.ai.

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