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Names & Taxonomy

Uniprot ID:: O15530
Entry Name:: PDPK1_HUMAN
Status:: reviewed
Protein Names:: 3-phosphoinositide-dependent protein kinase 1 (hPDK1) (EC 2.7.11.1)
Gene Names:: PDPK1 PDK1
Gene Names Primary:: PDPK1
Organism:: Homo sapiens (Human)

Structure

Length:: 556
Sequence:: MARTTSQLYDAVPIQSSVVLCSCPSPSMVRTQTESSTPPGIPGGSRQGPAMDGTAAEPRPGAGSLQHAQPPPQPRKKRPEDFKFGKILGEGSFSTVVLARELATSREYAIKILEKRHIIKENKVPYVTRERDVMSRLDHPFFVKLYFTFQDDEKLYFGLSYAKNGELLKYIRKIGSFDETCTRFYTAEIVSALEYLHGKGIIHRDLKPENILLNEDMHIQITDFGTAKVLSPESKQARANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKLEYDFPEKFFPKARDLVEKLLVLDATKRLGCEEMEGYGPLKAHPFFESVTWENLHQQTPPKLTAYLPAMSEDDEDCYGNYDNLLSQFGCMQVSSSSSSHSLSASDTGLPQRSGSNIEQYIHDLDSNSFELDLQFSEDEKRLLLEKQAGGNPWHQFVENNLILKMGPVDKRKGLFARRRQLLLTEGPHLYYVDPVNKVLKGEIPWSQELRPEAKNFKTFFVHTPNRTYYLMDPSGNAHKWCRKIQEVWRQRYQSHPDAAVQ
Proteomes:: UP000005640

Subcellular location

Subcellular Location:: Cytoplasm. Nucleus. Cell membrane; Peripheral membrane protein. Cell junction, focal adhesion. Note=Tyrosine phosphorylation seems to occur only at the cell membrane. Translocates to the cell membrane following insulin stimulation by a mechanism that involves binding to GRB14 and INSR. SRC and HSP90 promote its localization to the cell membrane. Its nuclear localization is dependent on its association with PTPN6 and its phosphorylation at Ser-396. Restricted to the nucleus in neuronal cells while in non-neuronal cells it is found in the cytoplasm. The Ser-241 phosphorylated form is distributed along the perinuclear region in neuronal cells while in non-neuronal cells it is found in both the nucleus and the cytoplasm. IGF1 transiently increases phosphorylation at Ser-241 of neuronal PDPK1, resulting in its translocation to other cellular compartments. The tyrosine-phosphorylated form colocalizes with PTK2B in focal adhesions after angiotensin II stimulation.

Function

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.
Catalytic Activity:: ATP + a protein = ADP + a phosphoprotein.
Enzyme Regulation:: ENZYME REGULATION: 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.
Active Site:: ACT_SITE 205 205 Proton acceptor.
Cross Reference Drug Bank:: DB00482
Gene Ontology Go:: cell projection
cytoplasm
cytoplasmic, membrane-bounded vesicle
cytosol
focal adhesion
neuronal postsynaptic density
nucleoplasm
plasma membrane
3-phosphoinositide-dependent protein kinase activity
ATP binding
phospholipase activator activity
phospholipase binding
protein serine/threonine kinase activity
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-serine phosphorylation
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
Gene Ontology Biological Process:: 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-serine phosphorylation
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
Gene Ontology Molecular Function:: 3-phosphoinositide-dependent protein kinase activity
ATP binding
phospholipase activator activity
phospholipase binding
protein serine/threonine kinase activity
Gene Ontology Cellular Component:: cell projection
cytoplasm
cytoplasmic, membrane-bounded vesicle
cytosol
focal adhesion
neuronal postsynaptic density
nucleoplasm
plasma membrane
Keywords:: 3D-structure
ATP-binding
Acetylation
Activator
Alternative splicing
Cell junction
Cell membrane
Complete proteome
Cytoplasm
Direct protein sequencing
Kinase
Membrane
Nucleotide-binding
Nucleus
Phosphoprotein
Reference proteome
Serine/threonine-protein kinase
Transcription
Transcription regulation
Transferase
Ubl conjugation
Interacts With:: P31749; Q00005; Q8IUH5

Names & Taxonomy

Structure

Subcellular location

Function

Publication