3-phosphoinositide-dependent protein kinase 1

Details

Name
3-phosphoinositide-dependent protein kinase 1
Synonyms
  • 2.7.11.1
  • hPDK1
  • PDK1
Gene Name
PDPK1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0002373|3-phosphoinositide-dependent protein kinase 1
MARTTSQLYDAVPIQSSVVLCSCPSPSMVRTQTESSTPPGIPGGSRQGPAMDGTAAEPRP
GAGSLQHAQPPPQPRKKRPEDFKFGKILGEGSFSTVVLARELATSREYAIKILEKRHIIK
ENKVPYVTRERDVMSRLDHPFFVKLYFTFQDDEKLYFGLSYAKNGELLKYIRKIGSFDET
CTRFYTAEIVSALEYLHGKGIIHRDLKPENILLNEDMHIQITDFGTAKVLSPESKQARAN
SFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKLEYD
FPEKFFPKARDLVEKLLVLDATKRLGCEEMEGYGPLKAHPFFESVTWENLHQQTPPKLTA
YLPAMSEDDEDCYGNYDNLLSQFGCMQVSSSSSSHSLSASDTGLPQRSGSNIEQYIHDLD
SNSFELDLQFSEDEKRLLLEKQAGGNPWHQFVENNLILKMGPVDKRKGLFARRRQLLLTE
GPHLYYVDPVNKVLKGEIPWSQELRPEAKNFKTFFVHTPNRTYYLMDPSGNAHKWCRKIQ
EVWRQRYQSHPDAAVQ
Number of residues
556
Molecular Weight
63151.305
Theoretical pI
7.38
GO Classification
Functions
3-phosphoinositide-dependent protein kinase activity / ATP binding / phospholipase activator activity / phospholipase binding / protein serine/threonine kinase activity
Processes
actin cytoskeleton organization / activation of protein kinase B activity / blood coagulation / calcium-mediated signaling / cell migration / cellular response to epidermal growth factor stimulus / cellular response to insulin stimulus / epidermal growth factor receptor signaling pathway / extrinsic apoptotic signaling pathway / Fc-epsilon receptor signaling pathway / fibroblast growth factor receptor signaling pathway / focal adhesion assembly / hyperosmotic response / innate immune response / insulin receptor signaling pathway / intracellular signal transduction / negative regulation of cardiac muscle cell apoptotic process / negative regulation of protein kinase activity / negative regulation of toll-like receptor signaling pathway / negative regulation of transforming growth factor beta receptor signaling pathway / neurotrophin TRK receptor signaling pathway / peptidyl-threonine phosphorylation / phosphatidylinositol-mediated signaling / platelet activation / positive regulation of establishment of protein localization to plasma membrane / positive regulation of phospholipase activity / positive regulation of release of sequestered calcium ion into cytosol / protein autophosphorylation / protein phosphorylation / regulation of endothelial cell migration / regulation of I-kappaB kinase/NF-kappaB signaling / regulation of mast cell degranulation / regulation of transcription, DNA-templated / small GTPase mediated signal transduction / stimulatory C-type lectin receptor signaling pathway / synaptic transmission / T cell costimulation / T cell receptor signaling pathway / transcription, DNA-templated / type B pancreatic cell development / vascular endothelial growth factor receptor signaling pathway
Components
cell projection / cytoplasm / cytoplasmic membrane-bounded vesicle / cytosol / focal adhesion / neuronal postsynaptic density / nucleoplasm / plasma membrane
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases. Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated kinase-1 (PAK1), protein kinase PKN (PKN1 and PKN2). Plays a central role in the transduction of signals from insulin by providing the activating phosphorylation to PKB/AKT1, thus propagating the signal to downstream targets controlling cell proliferation and survival, as well as glucose and amino acid uptake and storage. Negatively regulates the TGF-beta-induced signaling by: modulating the association of SMAD3 and SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the translocation of SMAD7 from the nucleus to the cytoplasm in response to TGF-beta. Activates PPARG transcriptional activity and promotes adipocyte differentiation. Activates the NF-kappa-B pathway via phosphorylation of IKKB. The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II. Controls proliferation, survival, and growth of developing pancreatic cells. Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells. Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis. Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response. Plays an important role during thymocyte development by regulating the expression of key nutrient receptors on the surface of pre-T cells and mediating Notch-induced cell growth and proliferative responses. Provides negative feedback inhibition to toll-like receptor-mediated NF-kappa-B activation in macrophages. Isoform 3 is catalytically inactive.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0021289|3-phosphoinositide-dependent protein kinase 1 (PDPK1)
ATGGCCAGGACCACCAGCCAGCTGTATGACGCCGTGCCCATCCAGTCCAGCGTGGTGTTA
TGTTCCTGCCCATCCCCATCAATGGTGAGGACCCAGACTGAGTCCAGCACGCCCCCTGGC
ATTCCTGGTGGCAGCAGGCAGGGCCCCGCCATGGACGGCACTGCAGCCGAGCCTCGGCCC
GGCGCCGGCTCCCTGCAGCATGCCCAGCCTCCGCCGCAGCCTCGGAAGAAGCGGCCTGAG
GACTTCAAGTTTGGGAAAATCCTTGGGGAAGGCTCTTTTTCCACGGTTGTCCTGGCTCGA
GAACTGGCAACCTCCAGAGAATATGCGATTAAAATTCTGGAGAAGCGACATATCATAAAA
GAGAACAAGGTCCCCTATGTAACCAGAGAGCGGGATGTCATGTCGCGCCTGGATCACCCC
TTCTTTGTTAAGCTTTACTTCACATTTCAGGACGACGAGAAGCTGTATTTCGGCCTTAGT
TATGCCAAAAATGGAGAACTACTTAAATATATTCGCAAAATCGGTTCATTCGATGAGACC
TGTACCCGATTTTACACGGCTGAGATTGTGTCTGCTTTAGAGTACTTGCACGGCAAGGGC
ATCATTCACAGGGACCTTAAACCGGAAAACATTTTGTTAAATGAAGATATGCACATCCAG
ATCACAGATTTTGGAACAGCAAAAGTCTTATCCCCAGAGAGCAAACAAGCCAGGGCCAAC
TCATTCGTGGGAACAGCGCAGTACGTTTCTCCAGAGCTGCTCACGGAGAAGTCCGCCTGT
AAGAGTTCAGACCTTTGGGCTCTTGGATGCATAATATACCAGCTTGTGGCAGGACTCCCA
CCATTCCGAGCTGGAAACGAGTATCTTATATTTCAGAAGATCATTAAGTTGGAATATGAC
TTTCCAGAAAAATTCTTCCCTAAGGCAAGAGACCTCGTGGAGAAACTTTTGGTTTTAGAT
GCCACAAAGCGGTTAGGCTGTGAGGAAATGGAAGGATACGGACCTCTTAAAGCACACCCG
TTCTTCGAGTCCGTCACGTGGGAGAACCTGCACCAGCAGACGCCTCCGAAGCTCACCGCT
TACCTGCCGGCTATGTCGGAAGACGACGAGGACTGCTATGGCAATTATGACAATCTCCTG
AGCCAGTTTGGCTGCATGCAGGTGTCTTCGTCCTCCTCCTCACACTCCCTGTCAGCCTCC
GACACGGGCCTGCCCCAGAGGTCAGGCAGCAACATAGAGCAGTACATTCACGATCTGGAC
TCGAACTCCTTTGAACTGGACTTACAGTTTTCCGAAGATGAGAAGAGGTTGTTGTTGGAG
AAGCAGGCTGGCGGAAACCCTTGCCTAACAGGACGTATTATCTGA
Chromosome Location
16
Locus
16p13.3
External Identifiers
ResourceLink
UniProtKB IDO15530
UniProtKB Entry NamePDPK1_HUMAN
GenBank Protein ID2407613
GenBank Gene IDAF017995
GenAtlas IDPDPK1
HGNC IDHGNC:8816
General References
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  2. Alessi DR, Deak M, Casamayor A, Caudwell FB, Morrice N, Norman DG, Gaffney P, Reese CB, MacDougall CN, Harbison D, Ashworth A, Bownes M: 3-Phosphoinositide-dependent protein kinase-1 (PDK1): structural and functional homology with the Drosophila DSTPK61 kinase. Curr Biol. 1997 Oct 1;7(10):776-89. [PubMed:9368760]
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  9. Pullen N, Dennis PB, Andjelkovic M, Dufner A, Kozma SC, Hemmings BA, Thomas G: Phosphorylation and activation of p70s6k by PDK1. Science. 1998 Jan 30;279(5351):707-10. [PubMed:9445476]
  10. Casamayor A, Morrice NA, Alessi DR: Phosphorylation of Ser-241 is essential for the activity of 3-phosphoinositide-dependent protein kinase-1: identification of five sites of phosphorylation in vivo. Biochem J. 1999 Sep 1;342 ( Pt 2):287-92. [PubMed:10455013]
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  12. Jensen CJ, Buch MB, Krag TO, Hemmings BA, Gammeltoft S, Frodin M: 90-kDa ribosomal S6 kinase is phosphorylated and activated by 3-phosphoinositide-dependent protein kinase-1. J Biol Chem. 1999 Sep 17;274(38):27168-76. [PubMed:10480933]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00482Celecoxibapproved, investigationalunknowninhibitorDetails
DB019337-Hydroxystaurosporineexperimental, investigationalunknownDetails
DB019463-[1-(3-Aminopropyl)-1h-Indol-3-Yl]-4-(1-Methyl-1h-Indol-3-Yl)-1h-Pyrrole-2,5-DioneexperimentalunknownDetails
DB02010StaurosporineexperimentalunknownDetails
DB04522DexfosfoserineexperimentalunknownDetails
DB0693210,11-dimethoxy-4-methyldibenzo[c,f]-2,7-naphthyridine-3,6-diamineexperimentalunknownDetails
DB070335-HYDROXY-3-[(1R)-1-(1H-PYRROL-2-YL)ETHYL]-2H-INDOL-2-ONEexperimentalunknownDetails
DB071321-{2-OXO-3-[(1R)-1-(1H-PYRROL-2-YL)ETHYL]-2H-INDOL-5-YL}UREAexperimentalunknownDetails
DB073002-(1H-imidazol-1-yl)-9-methoxy-8-(2-methoxyethoxy)benzo[c][2,7]naphthyridin-4-amineexperimentalunknownDetails
DB03777Rbt205 InhibitorexperimentalunknownDetails
DB074563-(1H-indol-3-yl)-4-(1-{2-[(2S)-1-methylpyrrolidinyl]ethyl}-1H-indol-3-yl)-1H-pyrrole-2,5-dioneexperimentalunknownDetails
DB074573-[1-(3-AMINOPROPYL)-1H-INDOL-3-YL]-4-(1H-INDOL-3-YL)-1H-PYRROLE-2,5-DIONEexperimentalunknownDetails
DB01863Inositol 1,3,4,5-TetrakisphosphateexperimentalunknownDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails