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Symbol PDPK1 contributors: mct/npt/pgu - updated : 01-02-2016
HGNC name 3-phosphoinositide dependent protein kinase-1
HGNC id 8816
Location 16p13.3      Physical location : 2.587.969 - 2.653.188
Synonym name PkB kinase like gene 1
Synonym symbol(s) PDK1, PRO0461, MGC20087, MGC35290, PkB-like, PkB-like 1
TYPE functioning gene
STRUCTURE 65.23 kb     14 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
14 - 7254 63 556 - 2008 18024423
11 - 6873 48 429 - 2008 18024423
isoform 2
12 - 7032 - 454 - 2008 18024423
Type ubiquitous
   expressed in (based on citations)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveintestinelarge intestinecolon highly Homo sapiens
Lymphoid/Immunelymph node   highly
Nervousnervecranial nerve  highly
SystemCellPubmedSpeciesStageRna symbol
Digestiveenterocyte Homo sapiens
cell lineage
cell lines
  • serine/threonine kinase monomeric enzyme
  • a catalytic domain similar to protein kinase A, B or C
  • a carboxy-terminal pleckstrin homology (PH) domain
  • conjugated PhosphoP
    interspecies homolog to Drosophila DSTPK61 kinase
    ortholog to murine Pdpk1
    ortholog to rattus Pdpk1
  • protein kinase superfamily
  • AGC Ser/Thr protein kinase family
  • PDK1 subfamily
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
  • translocating to the plasma membrane upon tyrosine-phosphorylation
  • in intestinal crypt enterocytes PDPK1 distributes to an apical membrane compartment comprising plasma membrane and apical endosomes, which, in turn, are in close contact with intermediate filaments
  • increased nuclear accumulation of PDPK1 in cells with enhanced PI3K activity
  • basic FUNCTION
  • 3-phosphoinositide (PtdIns(3,4,5)P3, PtdIns(3,4)P2)-dependent kinase 1
  • playing a central role in cellular signaling by phosphorylating members of the AGC family of kinases, including PKB/Akt
  • essential for the motility of vascular endothelial cells (ECs) and involved in the regulation of their chemotaxis
  • likely mediating the activation of protein-kinase B AKT/PKB, several PKC isotypes and SGK1, by insulin or growth factors
  • may playing a general role in signaling processes and in development
  • playing a critical role by nucleating the TCR-induced NF-kappaB activation pathway in T cells
  • PDPK1 signaling pathway plays an important role in regulating glucose homoeostasis and controlling expression of insulin-regulated genes
  • play a central regulatory role in many cell signalings between phosphoinositide-3 kinase and various intracellular serine/threonine kinases
  • PDPK1 plays an important role in cell proliferation and cell cycle progression by controlling the expression of both cyclin D1 and CDKN1B
  • plays a critical role in cardiac homeostasis in vivo by serving as a dual effector for cell survival and beta-adrenergic response
  • pivotal effector with dual functions to promote survival of cardiomyocytes and to preserve beta-AR response
  • in oocytes is required to maintain the survival of primordial follicles (PDPK1 signaling in oocytes plays an essential role in preserving the normal reproductive lifespan in females by maintaining the survival of primordial follicles during their long dormancy)
  • essential role in cardiovascular development through activation of AKT1 and SNAI1
  • in the context of cancer, role in anchorage-independent cell growth, migration, and invasion
  • PDPK1 and PLCG1 are two key enzymes in signal transduction that control several intracellular processes
  • role for nuclear-translocated PDPK1 in oncogenic cellular transformation and tumor progression
  • controls the activation of a subset of AGC kinases
  • is indispensable for B cell survival, proliferation, and growth regulation
  • act as a downstream effector in PI3K signaling and has been implicated in the regulation of neutrophil migration
  • critical role for PDPK1 in transducing inhibitory signals on eosinophil effector function
  • is likely a transducer of PI3K signaling and activates multiple downstream effectors, thereby representing an essential hub coordinating signals coming from extracellular cues to the cytoskeletal machinery, the final executor of cell movement
  • is an important mediator of phosphatidylinositol 3-kinase (PI3K) signaling
  • is required for exercise-induced cardiac hypertrophy but does not contribute to exercise-induced increases in mitochondrial function
  • appropriate levels of membrane-associated PDPK1 are required for stabilization of apical junctions, which promotes cell elongation, during epithelial morphogenesis
  • CELLULAR PROCESS protein, post translation
  • PDPK1 signaling in oocytes controls reproductive aging and lifespan by manipulating the survival of primordial follicles
  • PDPK1-PLCG1 pathway is important for cancer cell invasion
  • a component
    small molecule nucleotide,
  • ATP
  • protein
  • USP4 is an enzyme that removes ubiquitin from PDPK1 in and co-localizes with PDPK1 at the plasma membrane when the two proteins are overexpressed, indicating direct deubiquitination
  • PDPK1 regulates PLCG1 activation in a mechanism involving association of the two enzymes and modulation of PLCG1 tyrosine phosphorylation
  • PIK3CA activates AKT1, independently of PDPK1, and AKT2 by cooperating with PDPK1 in the insulin signal transduction pathway linked to SLC2A4 translocation
  • PDKP1, a kinase upstream of MTOR, connects IL15 signaling to NFIL3
  • in response to TNF, PDPK1 could phosphorylate RPS6KA3 and activated RPS6KA3, then promoting the activation of NFKB1
  • cell & other
    Other regulation by Src involves tyrosine phosphorylation of PDPK1 and Src homology 2 domain binding
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --other  
    deficiency of the PDK1 pathway in the liver could contribute to development of diabetes, as well as to liver failure
    Variant & Polymorphism
    Candidate gene
    Therapy target
    cardiovascularaquiredheart failure
    up-regulation of PDPK1 in the heart may emerge as a potential therapeutic strategy for heart failure
  • Pdk1-null mice died at embryonic day 9.5 with multiple abnormalities, including lack of somites, forebrain, and neural crest-derived tissues
  • mouse strain that showed reduced levels of Pdk1 activity, these hypomorphic Pdk1 mice were viable and fertile, and insulin injection induced the normal phosph
  • orylation responses attributed to Pdk1 activation; nevertheless, these mice were 40 to 50 percent smaller than control animals
  • PDPK1 protein were significantly decreased in the failing hearts of murine models