Search results for PDK1

Showing 21 results out of 53

×

Species

Types

Compartments

Reaction types

Search properties

Species

Types

Compartments

Reaction types

Search properties

Protein (3 results from a total of 3)

Identifier: R-HSA-203944
Species: Homo sapiens
Compartment: mitochondrial matrix
Primary external reference: UniProt: PDK1: Q15118
Identifier: R-HSA-61459
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: PDPK1: O15530
Identifier: R-HSA-202210
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: O15530

Reaction (4 results from a total of 31)

Identifier: R-HSA-202164
Species: Homo sapiens
Compartment: cytosol, plasma membrane
PI3K activation results in recruitment of the serine/threonine kinase PDK1, (3-phosphoinositide-dependent kinase 1) to the plasma membrane where PDK1 subsequently phosphorylates and activates AKT. PDK1 with its PH domain binds to either PIP3 or PIP2 and is translocated to the plasma membrane. PDK1 seems to exist in an active, phosphorylated configuration under basal conditions (Vanhaesebroeck & Alessi 2000).
Identifier: R-HSA-5218821
Species: Homo sapiens
Compartment: plasma membrane, cytosol
Protein kinase C (PKC) activation enhances angiogenesis by participating in the intracellular signaling of vascular endothelial growth factor (VEGF) in endothelial cells. VEGF can activate several PKC isoforms including alpha, beta, delta and zeta isoforms. Their activation is preceded by the activation of PLC gamma (Suzuma et al. 2002, Xia et al. 1996, Takahashi et al. 1999, Wellner et al. 1999). Before Protein kinase C (PKC) is competent to respond to second messengers it must first be phosphorylated at three conserved positions: the activation loop and two positions at the carboxyl terminus of the protein (Dutil et al. 1998). The phosphorylation of the activation loop appears to occur first and is mediated by phosphoinositide dependent protein kinases (PDKs). PDK1 phosphorylates PKCs at a critical Thr (T) residue in the activation loop, a requirement for PKC to gain catalytic competency (Toker 2003).
Identifier: R-HSA-9603279
Species: Homo sapiens
Compartment: cytosol, plasma membrane
Phosphatidylinositides generated by PI3K recruit phosphatidylinositide-dependent protein kinase 1 (PDK1) and AKT (also known as protein kinase B) to the membrane, through their PH (pleckstrin-homology) domains. The binding of PIP3 to the PH domain of AKT is the rate-limiting step in AKT activation. In mammals there are three AKT isoforms (AKT1-3) encoded by three separate genes. The three isoforms share a high degree of amino acid identity and have indistinguishable substrate specificity in vitro. However, isoform-preferred substrates in vivo cannot be ruled out. The relative expression of the three isoforms differs in different mammalian tissues: AKT1 is the predominant isoform in the majority of tissues, AKT2 is the predominant isoform in insulin-responsive tissues, and AKT3 is the predominant isoform in brain and testes. All 3 isoforms are expressed in human and mouse platelets (Yin et al. 2008; O'Brien et al. 2008). Note: all data in the pathway refer to AKT1, which is the most studied.
Identifier: R-HSA-6795473
Species: Homo sapiens
Compartment: cytosol, plasma membrane
PDPK1 (PDK1) activates SGK1 by phosphorylating threonine residue T256, located in the activation loop of SGK1. Phosphorylation of SGK1 at S422 facilitates subsequent phosphorylation at T256 (Kobayashi and Cohen 1999).

Complex (4 results from a total of 4)

Identifier: R-HSA-202349
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-198360
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-202311
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-377179
Species: Homo sapiens
Compartment: plasma membrane

Interactor (2 results from a total of 2)

Identifier: O15530-4
Species: Homo sapiens
Primary external reference: UniProt: O15530-4
Identifier: Q8N165
Species: Homo sapiens
Primary external reference: UniProt: Q8N165

Set (3 results from a total of 3)

Identifier: R-HSA-432180
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-419057
Species: Homo sapiens
Compartment: cytosol
ROCK I (alternatively called ROK ?) and ROCK II (also known as Rho kinase or ROK ?) were originally isolated as RhoA-GTP interacting proteins. The kinase domains of ROCK I and ROCK II are 92% identical, and so far there is no evidence that they phosphorylate different substrates. RhoA, RhoB, and RhoC associate with and activate ROCK but other GTP-binding proteins can be inhibitors, e.g. RhoE, Rad and Gem. PDK1 kinase promotes ROCK I activity not through phosphorylation but by blocking RhoE association. PLK1 can phosphorylate ROCK II and this enhances the effect of RhoA. Arachidonic acid can activate ROCK independently of Rho.
Identifier: R-HSA-4687776
Species: Homo sapiens
Compartment: cytosol
ROCK I (alternatively called ROK ?) and ROCK II (also known as Rho kinase or ROK ?) were originally isolated as RhoA-GTP interacting proteins. The kinase domains of ROCK I and ROCK II are 92% identical, and so far there is no evidence that they phosphorylate different substrates. RhoA, RhoB, and RhoC associate with and activate ROCK but other GTP-binding proteins can be inhibitors, e.g. RhoE, Rad and Gem. PDK1 kinase promotes ROCK I activity not through phosphorylation but by blocking RhoE association. PLK1 can phosphorylate ROCK II and this enhances the effect of RhoA. Arachidonic acid can activate ROCK independently of Rho.

Pathway (4 results from a total of 9)

Identifier: R-HSA-5625740
Species: Homo sapiens
Protein kinases N (PKN), also known as protein kinase C-related kinases (PKR) feature a C-terminal serine/threonine kinase domain and three RHO-binding motifs at the N-terminus. RHO GTPases RHOA, RHOB, RHOC and RAC1 bind PKN1, PKN2 and PKN3 (Maesaki et al. 1999, Zhong et al. 1999, Owen et al. 2003, Modha et al. 2008, Hutchinson et al. 2011, Hutchinson et al. 2013), bringing them in proximity to the PIP3-activated co-activator PDPK1 (PDK1) (Flynn et al. 2000, Torbett et al. 2003). PDPK1 phosphorylates PKNs on a highly conserved threonine residue in the kinase activation loop, which is a prerequisite for PKN activation. Phosphorylation of other residues might also be involved in activation (Flynn et al. 2000, Torbett et al. 2003, Dettori et al. 2009). PKNs are activated by fatty acids like arachidonic acid and phospholipids in vitro, but the in vivo significance of this activation remains unclear (Palmer et al. 1995, Yoshinaga et al. 1999).

PKNs play important roles in diverse functions, including regulation of cell cycle, receptor trafficking, vesicle transport and apoptosis. PKN is also involved in the ligand-dependent transcriptional activation by the androgen receptor. More than 20 proteins and several peptides have been shown to be phosphorylated by PKN1 and PKN2, including CPI-17 (Hamaguchi et al. 2000), alpha-actinin (Mukai et al. 1997), adducin (Collazos et al. 2011), CDC25C (Misaki et al. 2001), vimentin (Matsuzawa et al. 1997), TRAF1 (Kato et al. 2008), CLIP170 (Collazos et al. 2011) and EGFR (Collazos et al. 2011). There are no known substrates for PKN3 (Collazos et al. 2011).

Identifier: R-HSA-109703
Species: Homo sapiens
PKB and PDK1 are activated via membrane-bound PIP3. Activated PDK1 phosphorylates PKB, which in turn phosphorylates PDE3B. The latter hydrolyses cAMP to 5'AMP, depleting cAMP pools.
Identifier: R-HSA-1168372
Species: Homo sapiens
Compartment: cytosol, nucleoplasm
Second messengers (calcium, diacylglycerol, inositol 1,4,5-trisphosphate, and phosphatidyinositol 3,4,5-trisphosphate) trigger signaling pathways: NF-kappaB is activated via protein kinase C beta, RAS via RasGRP proteins, NF-AT via calcineurin, and AKT via PDK1 (reviewed in Shinohara and Kurosaki 2009, Stone 2006).
Identifier: R-HSA-202424
Species: Homo sapiens
Changes in gene expression are required for the T cell to gain full proliferative competence and to produce effector cytokines. Three transcription factors in particular have been found to play a key role in TCR-stimulated changes in gene expression, namely NFkappaB, NFAT and AP-1. A key step in NFkappaB activation is the stimulation and translocation of PRKCQ. The critical element that effects PRKCQ activation is PI3K. PI3K translocates to the plasma membrane by interacting with phospho-tyrosines on CD28 via its two SH2 domains located in p85 subunit (step 24). The p110 subunit of PI3K phosphorylates the inositol ring of PIP2 to generate PIP3 (steps 25). The reverse dephosphorylation process from PIP3 to PIP2 is catalysed by PTEN (step 27). PIP3 may also be dephosphorylated by the phosphatase SHIP to generate PI-3,4-P2 (step 26). PIP3 and PI-3,4-P2 acts as binding sites to the PH domain of PDK1 (step 28) and AKT (step 29). PKB is activated in response to PI3K stimulation by PDK1 (step 30). PDK1 has an essential role in regulating the activation of PRKCQ and recruitment of CBM complex to the immune synapse. PRKCQ is a member of novel class (DAG dependent, Ca++ independent) of PKC and the only member known to translocate to this synapse. Prior to TCR stimulation PRKCQ exists in an inactive closed conformation. TCR signals stimulate PRKCQ (step 31) and release DAG molecules. Subsequently, DAG binds to PRKCQ via the C1 domain and undergoes phosphorylation on tyrosine 90 by LCK to attain an open conformation (step 32). PRKCQ is further phosphorylated by PDK1 on threonine 538 (step 33). This step is critical for PKC activity. CARMA1 translocates to the plasma membrane following the interaction of its SH3 domain with the 'PxxP' motif on PDK1 (step 34). CARMA1 is phosphorylated by PKC-theta on residue S552 (step 35), leading to the oligomerization of CARMA1. This complex acts as a scaffold, recruiting BCL10 to the synapse by interacting with their CARD domains (step 36). BCL10 undergoes phosphorylation mediated by the enzyme RIP2 (step 37). Activated BCL10 then mediates the ubiquitination of IKBKG by recruiting MALT1 and TRAF6. MALT1 binds to BCL10 with its Ig-like domains and undergoes oligomerization (step 38). TRAF6 binds to the oligomerized MALT1 and also undergoes oligomerization (step 39). Oligomerized TRAF6 acts as a ubiquitin-protein ligase, catalyzing auto-K63-linked polyubiquitination (step 40). This K-63 ubiquitinated TRAF6 activates MAP3K7 kinase bound to TAB2 (step 41) and also ubiquitinates IKBKG in the IKK complex (step 44). MAP3K7 undergoes autophosphorylation on residues T184 and T187 and gets activated (step 42). Activated MAP3K7 kinase phosphorylates IKBKB on residues S177 and S181 in the activation loop and activates the IKK kinase activity (step 43). IKBKB phosphorylates the NFKBIA bound to the NFkappaB heterodimer, on residues S19 and S23 (step 45) and directs NFKBIA to 26S proteasome degradation (step 47). The NFkappaB heterodimer with a free NTS sequence finally migrates to the nucleus to regulate gene transcription (step 46).

Icon (1 results from a total of 1)

Species: Homo sapiens
3-phosphoinositide-dependent protein kinase 1
Cite Us!