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PDK1


Official Full Name
pyruvate dehydrogenase kinase 1
Organism
Homo sapiens
Gene ID
5163
Background
Pyruvate dehydrogenase (PDH) is a mitochondrial multienzyme complex that catalyzes the oxidative decarboxylation of pyruvate and is one of the major enzymes responsible for the regulation of homeostasis of carbohydrate fuels in mammals. The enzymatic activity is regulated by a phosphorylation/dephosphorylation cycle. Phosphorylation of PDH by a specific pyruvate dehydrogenase kinase (PDK) results in inactivation. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2013]
Synonyms
PDK1; pyruvate dehydrogenase kinase, isozyme 1; pyruvate dehydrogenase kinase, isoenzyme 1; mitochondrial pyruvate dehydrogenase, lipoamide, kinase isoenzyme 1
Bio Chemical Class
Kinase
Protein Sequence
MRLARLLRGAALAGPGPGLRAAGFSRSFSSDSGSSPASERGVPGQVDFYARFSPSPLSMKQFLDFGSVNACEKTSFMFLRQELPVRLANIMKEISLLPDNLLRTPSVQLVQSWYIQSLQELLDFKDKSAEDAKAIYDFTDTVIRIRNRHNDVIPTMAQGVIEYKESFGVDPVTSQNVQYFLDRFYMSRISIRMLLNQHSLLFGGKGKGSPSHRKHIGSINPNCNVLEVIKDGYENARRLCDLYYINSPELELEELNAKSPGQPIQVVYVPSHLYHMVFELFKNAMRATMEHHANRGVYPPIQVHVTLGNEDLTVKMSDRGGGVPLRKIDRLFNYMYSTAPRPRVETSRAVPLAGFGYGLPISRLYAQYFQGDLKLYSLEGYGTDAVIYIKALSTDSIERLPVYNKAAWKHYNTNHEADDWCVPSREPKDMTTFRSA
Open
Disease
Idiopathic interstitial pneumonitis, Inborn energy metabolism error, Insulin-resistance syndrome, Metastatic tumour, Solid tumour/cancer
Approved Drug
0
Clinical Trial Drug
1 +
Discontinued Drug
0

Cat.No. Product Name Price
SHH373012 shRNA set against Rat PDPK1 (NM_031081.1) Inquiry
SHR102300 shRNA set against Mouse Pdpk1(NM_001080773.1) Inquiry
SHR103062 shRNA set against Rat Pdpk1(NM_031081.1) Inquiry
SHW000846 shRNA set against Chicken PDPK1 (NM_001012529) Inquiry
SHH365820 shRNA set against Rat Olr754 (NM_001000368.1) Inquiry
SHH372864 shRNA set against Human PDK1 (NM_002610.3) Inquiry
SHH372868 shRNA set against Mouse PDK1 (NM_172665.4) Inquiry
SHH372872 shRNA set against Rat PDK1 (NM_053826.2) Inquiry
SHH373008 shRNA set against Mouse PDPK1 (NM_011062.4) Inquiry
SHR067656 shRNA set against Rat Olr77_predicted(NM_001001287.1) Inquiry
SHR102228 shRNA set against Rat Pdk1(NM_053826.2) Inquiry
SHR102264 shRNA set against Human PDK1(NM_002610.3) Inquiry
SHR102354 shRNA set against Mouse Pdpk1(NM_011062.4) Inquiry
SHW001947 shRNA set against Chicken PDK1 (NM_001031352) Inquiry
Cat.No. Product Name Price
CDFH013992 Human PDK1 cDNA Clone(NM_002610.3) Inquiry
MiUTR1R-05733 PDK1 miRNA 3'UTR clone Inquiry
MiUTR1R-05377 OLR754 miRNA 3'UTR clone Inquiry
MiUTR1M-09077 PDPK1 miRNA 3'UTR clone Inquiry
MiUTR1H-07755 PDPK1 miRNA 3'UTR clone Inquiry
MiUTR1H-07754 PDPK1 miRNA 3'UTR clone Inquiry
MiUTR1H-07753 PDPK1 miRNA 3'UTR clone Inquiry
MiUTR1H-07744 PDK1 miRNA 3'UTR clone Inquiry
CDFR013563 Rat Pdk1 cDNA Clone(NM_053826.2) Inquiry
CDFR012552 Rat Pdpk1 cDNA Clone(NM_031081.1) Inquiry
CDFR000360 Rat Olr754 cDNA Clone(NM_001000368.1) Inquiry
CDFH013993 Human PDK1 cDNA Clone(NM_002610.3) Inquiry
MiUTR1R-05742 PDPK1 miRNA 3'UTR clone Inquiry
SKO0199 PDK1 Validated sgRNA vector Inquiry
CDCL185686 Mouse PDPK1 ORF clone(NM_011062.4) Inquiry
CDCB162321 Chicken PDPK1 ORF Clone (NM_001012529) Inquiry
CDFG018719 Mouse Pdpk1 cDNA Clone(NM_001080773.1) Inquiry
CDCS410862 Human PDK1 ORF Clone (BC039158) Inquiry
CDCR380595 Rat Pdk1 ORF Clone(NM_053826.2) Inquiry
CDCR379574 Rat Pdpk1 ORF Clone(NM_031081.1) Inquiry
CDCR367437 Rat Olr754 ORF Clone(NM_001000368.1) Inquiry
CDCR283606 Human PDK1 ORF Clone(NM_002610.3) Inquiry
CDCL147783 Mouse Pdpk1 ORF clone (NM_001080773.1) Inquiry
CDCL147663 Mouse Pdk1 ORF clone (NM_172665.4) Inquiry
CDCB187082 Rabbit PDK1 ORF clone (XM_008258748.1) Inquiry
CDCB163422 Chicken PDK1 ORF Clone (NM_001031352) Inquiry
CDCB160100 Human PDK1 ORF clone (BC039158) Inquiry

Detailed Information

Introduction

The serine-threonine kinase PDK1 (or PDPK1) is a key element of signaling transduction activated by extracellular ligands, which recognized as a key regulator of cell migration and chemotaxis by controlling numerous elements of signaling transduction and cytoskeletal dynamics. PDK1 has been proved to exist in different cell types and organisms including endothelial cells, mammary epithelial cells, smooth muscle cells, T lymphocytes and neutrophils. Furthermore, PDK1 gene ablation or silencing is associated with tumor progression in different cellular and experimental models.

PDK1 and the Cell Migration

PDK1 (an ancient and conserved protein kinase) is found throughout the entire eukaryotic domain, whose importance in vertebrates is reflected in its relevant physiological roles in embryonic development and adulthood. PDK1 is a member of the AGC kinase family (cAMP-dependent, cGMP-dependent and protein kinase C), which includes 60 serine-threonine kinases with a common phylogenetic origin. PDK1 is responsible for the phosphorylation and activation of several other AGC kinases, such as p70S6K, SGK, p90RSK and atypical PKC isoforms, and is initially characterized for the phosphorylation of Akt on threonine 308 in the activation loop, which is essential for its activation. PDK1 is mainly localized in the cytoplasm and able to translocate into the nucleus with a mechanism that involves the inhibition of its nuclear export sequence. Previous studies have shown that PDK1 can move to the plasma membrane, which is essential for its ability to regulate cell migration.

PDK1 and the Signaling Pathways of Cell Migration

It is reported that the binding of PDK1 to plasma membrane phospholipid PtdIns (3, 4, 5) P3 produced by means of PI3K activity is one prominent explanation of the relevant role of PDK1 in regulating cell migration. PDK1 and Akt share the ability to bind PtdIns (3,4,5) P3 through their PH domains. When they colocalize at the plasma membrane, PDK1 phosphorylates Akt activation loop on threonine 308. PAK1 can bind the small GTPases cdc42 and RAC1, which event could potentially colocalize PDK1 and PAK1 at the plasma membrane at the leading edge. Moreover, PAK1 was shown involved in the regulation of cell migration through its substrates LIMK, p41-ARC, filamin A.

PDK1 Control Different Hallmarks of Tumor Invasion

Tumors may be defined as a wide group of somatic diseases accompanied by the uncontrolled proliferation of cells. The ability to invade surrounding tissues is considered a distinctive feature of malign ones. It has been reported that PDK1 plays a crucial role in different processes involved in tumor invasion and dissemination. PI3K/PDK1/Akt signaling axis is also required to form functional invadopodia with proteolytic activity as shown by in vitro gelatin degradation, but PDK1 and Akt inhibition provides an effective tool to block invadopodia formation which is sustained by the active and oncogenic forms of p110α (E545K and H1047R). PDK1 is involved in the regulation of collective invasion in MCF10DCIS model of breast tumor by MRCKα signaling pathway, whose overexpression leads to the formation of multicellular invasive structures from MCF10DCIS spheroids in basement membrane gel.

Figure 1. PDK1 localizes at the leading edge of migrating cells by binding to PtdIns (3,4,5) P3 produced by PI3K. (http://dx.doi.org/10.1016/j.bbcan.2015.07.003)

References:

  1. Paolo Armando Gagliardi, Laura di Blasio and Luca Primoa. (2015) 'PDK1: A signaling hub for cell migration and tumor invasion', Biochimica et Biophysica Acta, 1856: 178-188.
  2. Paolo Armando Gagliardia, Alberto Puliafitoa and Luca Primo. (2018) 'PDK1: At the crossroad of cancer signaling pathways', Seminars in Cancer Biology, 48:27-35.
  3. Pau Castel, Haley Ellis, Ruzica Bago, Eneda Toska, Pedram Razavi, F. Javier Carmona, Srinivasaraghavan Kannan, Chandra S. Verma, Maura Dickler, Sarat Chandarlapaty, Edi Brogi, Dario R. Alessi, Jose Baselga and Maurizio Scaltriti. (2016) 'PDK1-SGK1 Signaling Sustains AKT-Independent mTORC1 Activation and Confers Resistance to PI3Ka Inhibition', Cancer Cell, 30:229-242.
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