Search results for PRKCQ

Showing 13 results out of 17

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Protein (5 results from a total of 9)

Identifier: R-HSA-202346
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: PRKCQ: Q04759
Identifier: R-HSA-58216
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: PRKCQ: Q04759
Identifier: R-HSA-2648997
Species: Homo sapiens
Compartment: photoreceptor disc membrane
Primary external reference: UniProt: PRKCQ: Q04759
Identifier: R-HSA-212526
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: PRKCQ: Q04759
Identifier: R-HSA-212514
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: PRKCQ: Q04759

DNA Sequence (1 results from a total of 1)

Identifier: R-HSA-8938148
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: ENSEMBL: ENSEMBL:ENSG00000065675

Reaction (2 results from a total of 2)

Identifier: R-HSA-8938158
Species: Homo sapiens
Compartment: nucleoplasm, cytosol
Binding of the RUNX1:CBFB complex to the promoter of the PRKCQ gene, encoding Protein kinase C theta type, stimulates PRKCQ transcription. RUNX1 mutants associated with inherited thrombocytopenia are unable to transactivate the PRKCQ gene. PRKCQ is important for the functioning of megakaryocytes and platelets, but is not megakaryocyte specific (Jalagadugula et al. 2011).
Identifier: R-HSA-8938150
Species: Homo sapiens
Compartment: nucleoplasm
The RUNX1:CBFB complex binds the promoter of the PRKCQ gene, encoding Protein kinase C theta type (Jalagadugula et al. 2011).

Complex (1 results from a total of 1)

Identifier: R-HSA-8938154
Species: Homo sapiens
Compartment: nucleoplasm

Pathway (3 results from a total of 3)

Identifier: R-HSA-8936459
Species: Homo sapiens
In human hematopoietic progenitors, RUNX1 and its partner CBFB are up-regulated at the onset of megakaryocytic differentiation and down-regulated at the onset of erythroid differentiation. The complex of RUNX1 and CBFB cooperates with the transcription factor GATA1 in the transactivation of megakaryocyte-specific genes. In addition, RUNX1 and GATA1 physically interact (Elagib et al. 2003), and this interaction involves the zinc finger domain of GATA1 (Xu et al. 2006). Other components of the RUNX1:CBFB activating complex at megakaryocytic promoters are GATA1 heterodimerization partner, ZFPM1 (FOG1), histone acetyltransferases EP300 (p300) and KAT2B (PCAF), the WDR5-containing histone methyltransferase MLL complex and the arginine methyltransferase PRMT1 (Herglotz et al. 2013). In the absence of PRMT1, the transcriptional repressor complex can form at megakaryocytic promoters, as RUNX1 that is not arginine methylated can bind to SIN3A/SIN3B co-repressors (Zhao et al. 2008). Besides SIN3A/SIN3B, the RUNX1:CBFB repressor complex at megakaryocytic promoters also includes histone deacetylase HDAC1 and histone arginine methyltransferase PRMT6 (Herglotz et al. 2013).
Megakaryocytic promoters regulated by the described RUNX1:CBFB activating and repressing complexes include ITGA2B, GP1BA, THBS1 and MIR27A (Herglotz et al. 2013). ITGA2B is only expressed in maturing megakaryocytes and platelets and is involved in platelet aggregation (Block and Poncz 1995). GP1BA is expressed at the cell surface membrane of maturing megakaryocytes and platelets and participates in formation of platelet plugs (Cauwenberghs et al. 2000, Jilma-Stohlawetz et al. 2003, Debili et al. 1990). THBS1 homotrimers contribute to stabilization of the platelet aggregate (Bonnefoy and Hoylaerts 2008). MIR27A is a negative regulator of RUNX1 mRNA translation and may be involved in erythroid/megakaryocytic lineage determination (Ben-Ami et al. 2009).
The RUNX1:CBFB complex stimulates transcription of the PF4 gene, encoding a component of platelet alpha granules (Aneja et al. 2011), the NR4A3 gene, associated with the familial platelet disorder (FPD) (Bluteau et al. 2011), the PRKCQ gene, associated with inherited thrombocytopenia (Jalagadugula et al. 2011), the MYL9 gene, involved in thrombopoiesis (Jalagadugula et al. 2010), and the NFE2 gene, a regulator of erythroid and megakaryocytic maturation and differentiation (Wang et al. 2010).
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).
Identifier: R-HSA-9012852
Species: Homo sapiens
Similar to NOTCH1, NOTCH3 is activated by delta-like and jagged ligands (DLL/JAG) expressed in trans on a neighboring cell. The activation triggers cleavage of NOTCH3, first by ADAM10 at the S2 cleavage site, then by gamma-secretase at the S3 cleavage site, resulting in the release of the intracellular domain of NOTCH3, NICD3, into the cytosol. NICD3 subsequently traffics to the nucleus where it acts as a transcriptional regulator. NOTCH3 expression pattern is more restricted than the expression patterns of NOTCH1 and NOTCH2, with predominant expression of NOTCH3 in vascular smooth muscle cells, lymphocytes and the nervous system (reviewed by Bellavia et al. 2008). Based on the study of Notch3 knockout mice, Notch3 is not essential for embryonic development or fertility (Krebs et al. 2003).

Germline gain-of-function NOTCH3 mutations are an underlying cause of the CADASIL syndrome - cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. CADASIL is characterized by degeneration and loss of vascular smooth muscle cells from the arterial wall, predisposing affected individuals to an early onset stroke (Storkebaum et al. 2011). NOTCH3 promotes survival of vascular smooth muscle cells at least in part by induction of CFLAR (c FLIP), an inhibitor of FASLG activated death receptor signaling. The mechanism of NOTCH3 mediated upregulation of CFLAR is unknown; it is independent of the NOTCH3 coactivator complex and involves an unelucidated crosstalk with the RAS/RAF/MAPK pathway (Wang et al. 2002).

In rat brain, NOTCH3 and NOTCH1 are expressed at sites of adult neurogenesis, such as the dentate gyrus (Irvin et al. 2001). NOTCH3, similar to NOTCH1, promotes differentiation of the rat adult hippocampus derived multipotent neuronal progenitors into astroglia (Tanigaki et al. 2001). NOTCH1, NOTCH2, NOTCH3, and their ligand DLL1 are expressed in neuroepithelial precursor cells in the neural tube of mouse embryos. Together, they signal to inhibit neuronal differentiation of neuroepithelial precursors. Expression of NOTCH3 in mouse neuroepithelial precursors is stimulated by growth factors BMP2, FGF2, Xenopus TGF beta5 - homologous to TGFB1, LIF, and NTF3 (Faux et al. 2001).

In mouse telencephalon, NOTCH3, similar to NOTCH1, promotes radial glia and neuronal progenitor phenotype. This can, at least in part be attributed to NOTCH mediated activation of RBPJ-dependent and HES5-dependent transcription (Dang et al. 2006).

In mouse spinal cord, Notch3 is involved in neuronal differentiation and maturation. Notch3 knockout mice have a decreased number of mature inhibitory interneurons in the spinal cord, which may be involved in chronic pain conditions (Rusanescu and Mao 2014).

NOTCH3 amplification was reported in breast cancer, where NOTCH3 promotes proliferation and survival of ERBB2 negative breast cancer cells (Yamaguchi et al. 2008), and it has also been reported in ovarian cancer (Park et al. 2006). NOTCH3 signaling is involved in TGF beta (TGFB1) signaling-induced eptihelial to mesenchimal transition (EMT) (Ohashi et al. 2011, Liu et al. 2014)

NOTCH3 indirectly promotes development of regulatory T cells (Tregs). NOTCH3 signaling activates pre-TCR-dependent and PKC-theta (PRKCQ)-dependent NF-kappaB (NFKB) activation, resulting in induction of FOXP3 expression (Barbarulo et al. 2011). Deregulated NOTCH3 and pre-TCR signaling contributes to development of leukemia and lymphoma (Bellavia et al. 2000, Bellavia et al. 2002).

Icon (1 results from a total of 1)

Species: Homo sapiens
Protein kinase C theta type
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