Abstract
Alongside Liver kinase B1 (LKB1) and Ca2+/Calmodulin-dependent protein kinase kinase 2 (CaMKK2), Transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) has been suggested as a direct upstream kinase of AMP-activated protein kinase (AMPK). Several subsequent studies have reported on the TAK1-AMPK relationship, but the interpretation of the respective data has led to conflicting views. Therefore, to date the acceptance of TAK1 as a genuine AMPK kinase is lagging behind. This review provides with argumentation, whether or not TAK1 functions as a direct upstream kinase of AMPK. Several specific open questions that may have precluded the consensus are discussed based on available data. In brief, TAK1 can function as direct AMPK upstream kinase in specific contexts and in response to a subset of TAK1 activating stimuli. Further research is needed to define the intricate signals that are conditional for TAK1 to phosphorylate and activate AMPKα at T172.
Highlights
This review provides with argumentation, whether or not TAK1 functions as a direct upstream kinase of AMPK
This review addresses questions that are relevant for experts in the field already familiar with AMPK and TAK1
TAK1 is activated by interleukin-1 (IL-1) and Transforming growth factor-β (TGF-β) receptors, tumour necrosis factor (TNF)-α, Toll-like receptors (TLR), CD40, and the B cell receptor
Summary
This review addresses questions that are relevant for experts in the field already familiar with AMPK and TAK1. TAK1 has been proposed as an alternative third AMPK kinase, which has received varying appreciation. This is the topic of this review. TAK1 is a serine/threonine protein kinase of the mitogen-activated protein kinase kinase kinase (MAP3K) family, playing a crucial role in regulating cell survival, differentiation, apoptosis, and inflammatory responses [15,16]. TAK1 has been described as a regulator of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and MAPKs in proinflammatory signalling. This picture has been significantly amended, with the roles of TAK1 in tissue homeostasis (reviewed in [17]), as further discussed below
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
