Serine 389 phosphorylation of 3-phosphoinositide-dependent kinase 1 by UNC-51-like kinase 1 affects its ability to regulate Akt and p70 S6kinase.

BMB Rep

Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141; Department of Bio-Molecular Science, KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon 34113, Korea.

Published: July 2020


Category Ranking

98%

Total Visits

921

Avg Visit Duration

2 minutes

Citations

20

Article Abstract

Phosphorylation of the signaling component by protein kinase often leads to a kinase cascade or feedback loop. 3-Phosphoinositide- dependent kinase 1 (PDK1) signaling pathway diverges into various kinases including Akt and p70 S6 kinase (p70S6k). However, the PDK1 feedback mechanism remains elusive. Here, we demonstrated that UNC-51-like kinase (ULK1), an autophagy initiator kinase downstream of mechanistic target of rapamycin (mTOR), directly phosphorylated PDK1 on serine 389 at the linker region. Furthermore, our data showed that this phosphorylation affected the kinase activity of PDK1 toward downstream substrates. These results suggest a possible negative feedback loop between PDK1 and ULK1. [BMB Reports 2020; 53(7): 373-378].

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396916PMC
http://dx.doi.org/10.5483/BMBRep.2020.53.7.299DOI Listing

Publication Analysis

Top Keywords

kinase
9
serine 389
8
unc-51-like kinase
8
akt p70
8
feedback loop
8
pdk1
5
389 phosphorylation
4
phosphorylation 3-phosphoinositide-dependent
4
3-phosphoinositide-dependent kinase
4
kinase unc-51-like
4

Similar Publications

Insights Into the Separate and Joint Effects of Cadmium and Cesium on the Risk of Circadian Syndrome and the Underlying Mechanism: An Integrated Epidemiological and Network Toxicological Study.

Biol Trace Elem Res

September 2025

Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science

The uncharted effects of cadmium and cesium on circadian syndrome (CircS), an emerging circadian rhythm disorder drawing considerable attention, and underlying mechanisms warrant exigent elaboration. Data of 11141 subjects from National Health and Nutrition Examination Survey 2005-2018 were incorporated to investigate separate-, joint-/interaction-, and mixture-effects of urinary cadmium and cesium on prevalent CircS risk exploiting survey weight regression and quantile g-computation. The underlying mechanisms were probed by network toxicological analysis.

View Article and Find Full Text PDF

The progression of renal fibrosis is difficult to reverse, and Poria cocos, one of the main components of Wenyang Zhenshuai Granules, has been shown to be crucial to the development of the epithelial-mesenchymal transition (EMT). This study aimed to examine the molecular mechanism by which Poricoic Acid A (PAA) inhibited the advancement of EMT in renal tubular epithelial (RTE) cells. The protein levels of sprouty RTK signaling antagonist 2 (SPRY2) extracellular regulated protein kinases (ERK), and p-ERK were measured.

View Article and Find Full Text PDF

Which came first - the messenger, the activator, or the receiver?

Trends Plant Sci

September 2025

Department of Plant and Environmental Sciences, Section of Transport Biology, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark. Electronic address:

Plants have developed sophisticated signaling mechanisms to adapt to environmental changes, and secreted peptides play crucial roles. Sulfated tyrosine (sTyr) peptides are important regulators of plant growth, nutrient uptake, defense responses, and seed development. This study delves into the evolution of sTyr peptides, their receptors, and the enzyme tyrosylprotein sulfotransferase (TPST) that is responsible for their activation.

View Article and Find Full Text PDF

This study investigated the effects of soy isoflavone yeast fermented extract (soyF) and soy isoflavone yeast unfermented extract (soyN) on rat ileal smooth muscle contraction. SoyF and soyN inhibited carbachol (CCh)- or KCl-induced contraction in a concentration-dependent manner; however, these effects were stronger for CCh-induced contraction than that for KCl, and the relaxation effect was stronger for soyF than for soyN. SoyF-induced relaxation was attenuated by 4-aminopyridine (4-AP), a Kv channel inhibitor, and iberiotoxin (IbTX), a calcium-activated potassium channel (BK channel) inhibitor.

View Article and Find Full Text PDF

Antigen-binding proteins, such as nanobodies, modified with functional small molecules hold great potential for applications including imaging probes, drug conjugates, and localized catalysts. However, traditional chemical labeling methods that randomly target lysine or cysteine residues often produce heterogeneous conjugates with limited reproducibility. Conventional site-specific conjugation approaches, which typically modify only the N- or C-terminus, may also be insufficient to achieve the desired functionalities.

View Article and Find Full Text PDF