PDPK1 - 3-phosphoinositide-dependent protein kinase 1 - human protein (Function)
 
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PDPK1 »  3-phosphoinositide-dependent protein kinase 1   [ EC 2.7.11.1 ]
 
Gene name:  PDPK1
Entry whose protein(s) existence is based on evidence at protein level
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1 180 5
GENE REF ISO

Function

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Overview 
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.  
15
  • CuratedUniProtKB
Isoform  Iso 3   Is catalytically inactive.  
15
  • CuratedUniProtKB
GO molecular function 
3-phosphoinositide-dependent protein kinase activitydefinition[GO:0004676]  
1
  • IDABHF-UCL
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Insulin receptor bindingdefinition[GO:0005158] silver  
  • IEAOrtholog Compara
Phospholipase activator activitydefinition[GO:0016004]  
1
  • IMPBHF-UCL
Phospholipase bindingdefinition[GO:0043274]  
1
  • IPIBHF-UCL
Protein bindingdefinition[GO:0005515]  
6
  • IPIIntAct
  • IPIUniProtKB
Protein kinase bindingdefinition[GO:0019901] silver  
  • IEAOrtholog Compara
Protein serine/threonine kinase activitydefinition[GO:0004674]  
1
  • IDABHF-UCL
GO biological process 
Actin cytoskeleton organizationdefinition[GO:0030036]  
1
  • TASPINC
Activation of protein kinase B activitydefinition[GO:0032148]  
1
  • IDABHF-UCL
Calcium-mediated signalingdefinition[GO:0019722]  
1
  • IMPBHF-UCL
Cell migrationdefinition[GO:0016477]  
1
  • IMPBHF-UCL
Cellular response to epidermal growth factor stimulusdefinition[GO:0071364]  
1
  • IMPBHF-UCL
Cellular response to insulin stimulusdefinition[GO:0032869]  
1
  • IMPBHF-UCL
Epidermal growth factor receptor signaling pathwaydefinition[GO:0007173]  
1
  • IMPBHF-UCL
Extrinsic apoptotic signaling pathwaydefinition[GO:0097191]  
1
  • IMPUniProtKB
Focal adhesion assemblydefinition[GO:0048041] silver  
  • IEAOrtholog Compara
Hyperosmotic responsedefinition[GO:0006972] silver  
  • IEAOrtholog Compara
Intracellular signal transductiondefinition[GO:0035556]  
1
  • IDAMGI
Negative regulation of cardiac muscle cell apoptotic processdefinition[GO:0010667] silver  
  • IEAOrtholog Compara
Negative regulation of protein kinase activitydefinition[GO:0006469]  
1
  • IDABHF-UCL
Negative regulation of toll-like receptor signaling pathwaydefinition[GO:0034122] silver  
  • IEAOrtholog Compara
Negative regulation of transforming growth factor beta receptor signaling pathwaydefinition[GO:0030512]  
1
  • IDAUniProtKB
Peptidyl-threonine phosphorylationdefinition[GO:0018107]  
1
  • IDABHF-UCL
Positive regulation of establishment of protein localization to plasma membranedefinition[GO:0090004]  
1
  • IMPBHF-UCL
Positive regulation of phospholipase activitydefinition[GO:0010518]  
1
  • IMPBHF-UCL
Positive regulation of release of sequestered calcium ion into cytosoldefinition[GO:0051281]  
1
  • IDABHF-UCL
Protein autophosphorylationdefinition[GO:0046777]  
1
  • TASUniProtKB
Protein phosphorylationdefinition[GO:0006468]  
1
  • IDAUniProtKB
Regulation of endothelial cell migrationdefinition[GO:0010594] silver  
  • IEAOrtholog Compara
Regulation of I-kappaB kinase/NF-kappaB signalingdefinition[GO:0043122]  
1
  • IMPUniProtKB
Regulation of mast cell degranulationdefinition[GO:0043304] silver  
  • IEAOrtholog Compara
Regulation of transcription, DNA-templateddefinition[GO:0006355]  
  • IEAUniProtKB KW
Transcription, DNA-templateddefinition[GO:0006351]  
  • IEAUniProtKB KW
Type B pancreatic cell developmentdefinition[GO:0003323] silver  
  • IEAOrtholog Compara
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.1: ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
It is regulated in the following manner
Homodimerization regulates its activity by maintaining the kinase in an autoinhibitory conformation. NPRL2 down-regulates its activity by interfering with tyrosine phosphorylation at the Tyr-9, Tyr-373 and Tyr-376 residues. The 14-3-3 protein YWHAQ acts as a negative regulator by association with the residues surrounding the Ser-241 residue. STRAP positively regulates its activity by enhancing its autophosphorylation and by stimulating its dissociation from YWHAQ. SMAD2, SMAD3, SMAD4 and SMAD7 also positively regulate its activity by stimulating its dissociation from YWHAQ. Activated by phosphorylation on Tyr-9, Tyr-373 and Tyr-376 by INSR in response to insulin.  
4
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Aldosterone-regulated sodium reabsorption  hsa04960+5170  
Endometrial cancer  hsa05213+5170  
Focal adhesion  hsa04510+5170  
Insulin signaling pathway  hsa04910+5170  
mTOR signaling pathway  hsa04150+5170  
Non-small cell lung cancer  hsa05223+5170  
PPAR signaling pathway  hsa03320+5170  
Prostate cancer  hsa05215+5170  
According to Reactome, this protein belongs to the following pathways:
Activation of PKB  REACT_790  
CD28 dependent PI3K/Akt signaling  REACT_19358  
Constitutive PI3K/AKT Signaling in Cancer  REACT_147727  
CTLA4 inhibitory signaling  REACT_19405  
Downstream TCR signaling  REACT_12555  
FCERI mediated NF-kB activation  REACT_163994  
G beta:gamma signalling through PI3Kgamma  REACT_19290  
GPVI-mediated activation cascade  REACT_1695  
Integrin alphaIIb beta3 signaling  REACT_15523  
PIP3 activates AKT signaling  REACT_75829  
Role of LAT2/NTAL/LAB on calcium mobilization  REACT_163769  
RSK activation  REACT_20510  
 

Keywords

Biological process 
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Molecular function 
Activator  definition   [KW-0010]
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: Phosphoinositide-dependent_kinase-1
GenomeRNAi: 5170
PRO: PR:O15530
Chemistry
GuidetoPHARMACOLOGY: 1519