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PDK1

GeneName

PDK1

Summary

PDK1, also known as 3-phosphoinositide dependent protein kinase 1 or PDHK1, is a 49 kDa protein that is primarily localised in the mitochondrial matrix and is a component of the pyruvate dehydrogenase complex. It plays a vital role in cellular metabolism by phosphorylating and inactivating the pyruvate dehydrogenase complex, thereby regulating the conversion of pyruvate to acetyl-CoA. PDK1 is involved in various biological pathways, including glucose metabolism and responses to oxidative stress, and is essential for the regulation of cell population proliferation and intrinsic apoptotic signalling pathways.

Importance

PDK1 is relevant to: - Metabolic regulation, particularly in cancer cells where altered glucose metabolism is a hallmark - The response to hypoxia through its role in the hypoxia-inducible factor-1alpha signalling pathway - The regulation of apoptosis in conditions of oxidative stress, impacting cell survival - The modulation of acetyl-CoA biosynthesis, which is critical for fatty acid and cholesterol synthesis

Top Products

For researchers investigating PDK1, we recommend two excellent primary antibodies. The first is the well-cited Anti-PDK1 antibody [4A11] (ab110025), which has garnered 51 citations and is highly regarded for its performance in Western blotting (WB), immunohistochemistry (IHC), immunocytochemistry (ICC), and flow cytometry (FC). This antibody is a reliable choice for various applications in PDK1 research.Additionally, we offer the recombinant antibody, Anti-PDK1 antibody [EPR19571] (ab202468), which has been validated in knockout models and is suitable for WB, ICC, flow cytometry (FC), and immunoprecipitation (IP). With 41 citations, this recombinant antibody provides the batch-to-batch consistency that many researchers seek, making it an excellent option for those requiring dependable PDK1 detection.

Abcam Product Citation Summary

The data indicates that PDK1 is being studied in various contexts, including brain injury, neurological impairment, glucose metabolism in heart failure, and diabetic kidney disease. The use of Abcam antibodies in both rat and human cell lines highlights the relevance of PDK1 in different biological systems and disease states.

Abcam Product Citation Table

Product Code
Species
Application
Study Context
PMID
ab110025
Rat
WB, IF
Brain injury
30867669
ab110025
Rat
WB, IF
Neurological impairment
30867669
ab110025
Rat
WB
Glucose metabolism in heart failure
32372956
ab110025
Mouse
WB
Glucose metabolism
32444604
ab110025
Human
WB
Regulation of PDK1 by miR-4290
32321153
ab110025
Human
WB
Glycolysis suppression
32321153
ab110025
Human
WB
Effect of AC093818.1
31988283
ab110025
Mouse
WB
Diabetic kidney disease
32444604
ab110335
Human
WB
Cell lines NB4 and THP-1
24506813

Function

Kinase that plays a key role in regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2 (PubMed:7499431, PubMed:18541534, PubMed:22195962, PubMed:26942675, PubMed:17683942). This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate (PubMed:18541534, PubMed:22195962, PubMed:26942675). Plays an important role in cellular responses to hypoxia and is important for cell proliferation under hypoxia (PubMed:18541534, PubMed:22195962, PubMed:26942675).

Post-translational modifications

Phosphorylated by constitutively activated ABL1, FGFR1, FLT3 and JAK2 (in vitro), and this may also occur in cancer cells that express constitutively activated ABL1, FGFR1, FLT3 and JAK2. Phosphorylation at Tyr-243 and Tyr-244 strongly increases kinase activity, while phosphorylation at Tyr-136 has a lesser effect (PubMed:22195962). Phosphorylated under hypoxic conditions at Thr-338 by phosphoglycerate kinase PGK1 which has an activating effect (PubMed:26942675).

Sequence Similarities

Belongs to the PDK/BCKDK protein kinase family.

Tissue Specificity

Expressed predominantly in the heart. Detected at lower levels in liver, skeletal muscle and pancreas.

Cellular localization

Alternative names

PDHK1, PDK1, Pyruvate dehydrogenase kinase isoform 1, PDH kinase 1

swissprot:Q15118 entrezGene:5166 entrezGene:5165 entrezGene:5164 entrezGene:5163 swissprot:Q16654 swissprot:Q15120 swissprot:Q15119 omim:602524