InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PDPK1

Summary

InnateDB Protein

IDBP-10654.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PDPK1

Protein Name

3-phosphoinositide dependent protein kinase-1

Synonyms

PDK1; PDPK2; PRO0461;

Species

Homo sapiens

Ensembl Protein

ENSP00000268673

InnateDB Gene

IDBG-10648 (PDPK1)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:10226025, ECO:0000269PubMed:10480933, ECO:0000269PubMed:10995762, ECO:0000269PubMed:12167717, ECO:0000269PubMed:14585963, ECO:0000269PubMed:14604990, ECO:0000269PubMed:16207722, ECO:0000269PubMed:16251192, ECO:0000269PubMed:17327236, ECO:0000269PubMed:17371830, ECO:0000269PubMed:18835241, ECO:0000269PubMed:9094314, ECO:0000269PubMed:9445476, ECO:0000269PubMed:9707564, ECO:0000269PubMed:9768361}.

Subcellular Localization

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.

Disease Associations

Tissue Specificity

Appears to be expressed ubiquitously. The Tyr- 9 phosphorylated form is markedly increased in diseased tissue compared with normal tissue from lung, liver, colon and breast. {ECO:0000269PubMed:18024423}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 94 experimentally validated interaction(s) in this database.
They are also associated with 14 interaction(s) predicted by orthology.

Experimentally validated
Total	94 [view]
Protein-Protein	93 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	14 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004676	3-phosphoinositide-dependent protein kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016004	phospholipase activator activity
GO:0016301	kinase activity
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0043274	phospholipase binding

Biological Process

GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0006468	protein phosphorylation
GO:0006469	negative regulation of protein kinase activity
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007268	synaptic transmission
GO:0007596	blood coagulation
GO:0008286	insulin receptor signaling pathway
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0010518	positive regulation of phospholipase activity
GO:0016477	cell migration
GO:0018107	peptidyl-threonine phosphorylation
GO:0019722	calcium-mediated signaling
GO:0030036	actin cytoskeleton organization
GO:0030168	platelet activation
GO:0030512	negative regulation of transforming growth factor beta receptor signaling pathway
GO:0031295	T cell costimulation
GO:0032148	activation of protein kinase B activity
GO:0032869	cellular response to insulin stimulus
GO:0035556	intracellular signal transduction
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0043122	regulation of I-kappaB kinase/NF-kappaB signaling
GO:0045087	innate immune response
GO:0046777	protein autophosphorylation
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048015	phosphatidylinositol-mediated signaling
GO:0050852	T cell receptor signaling pathway
GO:0051281	positive regulation of release of sequestered calcium ion into cytosol
GO:0071364	cellular response to epidermal growth factor stimulus
GO:0090004	positive regulation of establishment of protein localization to plasma membrane
GO:0097191	extrinsic apoptotic signaling pathway

Cellular Component

GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0005925	focal adhesion
GO:0042995	cell projection

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain

PFAM

PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00220

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt