AMPK-mediated phosphorylation enhances the auto-inhibition of TBC1D17 to promote Rab5-dependent glucose uptake

Rao, Xi; Cong, Xiao Xia; Gao, Xiu Kui; Shi, Yin; Shi, Lin; Wang, Jian Feng; Ni, Chen-Yao; He, Ming Fang; Xu, Yingke; Yi, Cong; Meng, Zhuo-Xian; Liu, Jinling; Peng, Lin; Zheng, Li; Zhou, Yi

doi:10.1038/s41418-021-00809-9

Cited by 24 publications

(18 citation statements)

References 78 publications

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“…AMP-activated protein kinase (AMPK) is a heterotrimeric protein kinase consisting of three subunits, α catalytic subunit and β as well as γ regulatory subunits, and mainly functions as an energy sensor to regulate metabolic homeostasis [ [12] , [13] , [14] ]. Emerging studies have revealed that AMPKα activation also suppresses inflammation and oxidative stress, and effectively prevents lung injury under different contexts [ [15] , [16] , [17] ].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Macrophage SAMSN1 protects against sepsis-induced acute lung injury in mice

Jiang

Bai

et al. 2022

Redox Biology

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Section: Introductionmentioning

confidence: 99%

RETRACTED: Macrophage SAMSN1 protects against sepsis-induced acute lung injury in mice

Jiang

Bai

et al. 2022

Redox Biology

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“…Cells were seeded on coverslips in 24-well plates and transfected with various expression constructs for 24–36 h. They were then stained for immunofluorescence detection using confocal fluorescence microscopy or directly visualized for cells expressing GFP or mCherry-tagged proteins as previously described 91 . Briefly, the cells were washed with PBSCM buffer (PBS buffer supplemented with 10 mM CaCl 2 and 10 mM MgCl 2 ) followed by fixation with 3% paraformaldehyde in PBSCM.…”

Section: Methodsmentioning

confidence: 99%

Phase separation of insulin receptor substrate 1 drives the formation of insulin/IGF-1 signalosomes

et al. 2022

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As a critical node for insulin/IGF signaling, insulin receptor substrate 1 (IRS-1) is essential for metabolic regulation. A long and unstructured C-terminal region of IRS-1 recruits downstream effectors for promoting insulin/IGF signals. However, the underlying molecular basis for this remains elusive. Here, we found that the C-terminus of IRS-1 undergoes liquid-liquid phase separation (LLPS). Both electrostatic and hydrophobic interactions were seen to drive IRS-1 LLPS. Self-association of IRS-1, which was mainly mediated by the 301–600 region, drives IRS-1 LLPS to form insulin/IGF-1 signalosomes. Moreover, tyrosine residues of YXXM motifs, which recruit downstream effectors, also contributed to IRS-1 self-association and LLPS. Impairment of IRS-1 LLPS attenuated its positive effects on insulin/IGF-1 signaling. The metabolic disease-associated G972R mutation impaired the self-association and LLPS of IRS-1. Our findings delineate a mechanism in which LLPS of IRS-1-mediated signalosomes serves as an organizing center for insulin/IGF-1 signaling and implicate the role of aberrant IRS-1 LLPS in metabolic diseases.

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“…Moreover, multiple proteins of cluster II (Fig. 1e) have been related to SnRK1 in other studies (see Supplementary Note), such as i) the cytosolic invertase CINV1, which mediates breakdown of sucrose into glucose and fructose and directly interacts with SnRK1 in Y2H 27 , ii) three homologs (AtO3L4/KCP, AtO3L1 & AtOXS3) of the SKIN protein, which negatively regulates SnRK1 in rice 17 , or iii) AtVPS9a and AT5G52580.1, homologs of human AMPK substrates that function in intracellular trafficking 28,29 .…”

Section: Sucrose Triggers Rapid Dephosphorylation Of Snrk1 Targetsmentioning

confidence: 96%

Mapping of the plant SnRK1 kinase signalling network reveals a key regulatory role for the class II T6P synthase-like proteins

et al. 2022

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The central metabolic regulator SnRK1 controls plant growth and survival upon activation by energy depletion, but detailed molecular insight into its regulation and downstream targets is limited. Here, we used phosphoproteomics to infer the sucrose-dependent processes targeted upon starvation by kinases as SnRK1, corroborating the relation of SnRK1 with metabolic enzymes and transcriptional regulators, while also pointing to SnRK1 control of intracellular trafficking. Next, we integrated affinity purification, proximity labeling and cross-linking mass spectrometry to map the protein interaction landscape, composition and structure of the SnRK1 heterotrimer, providing insight in its plant-specific regulation. At the intersection of this multi-dimensional interactome, we discovered a strong association of SnRK1 with Class II T6P synthase (TPS)-like proteins. Biochemical and cellular assays show that TPS-like proteins function as negative regulators of SnRK1. Next to stable interactions with the TPS-like proteins, similar intricate connections were found with known regulators, suggesting that plants utilize an extended kinase complex to fine-tune SnRK1 activity for optimal responses to metabolic stress.

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AMPK-mediated phosphorylation enhances the auto-inhibition of TBC1D17 to promote Rab5-dependent glucose uptake

Cited by 24 publications

References 78 publications

RETRACTED: Macrophage SAMSN1 protects against sepsis-induced acute lung injury in mice

RETRACTED: Macrophage SAMSN1 protects against sepsis-induced acute lung injury in mice

Phase separation of insulin receptor substrate 1 drives the formation of insulin/IGF-1 signalosomes

Mapping of the plant SnRK1 kinase signalling network reveals a key regulatory role for the class II T6P synthase-like proteins

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