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Vps34 stimulates tumor development mainly through PKC-delta- activation of p62.
Here we show that a putative fifth subunit, nuclear receptor binding factor 2 (NRBF2 (show NRBF2 Proteins)), is a tightly bound component of the class III phosphatidylinositol 3-kinase complex I that profoundly affects its activity and architecture. NRBF2 (show NRBF2 Proteins) is a homodimer and drives the dimerization of the larger PI3KC3-C1 complex, with implications for the higher-order organization of the preautophagosomal structure.
This study reveals NRBF2 (show NRBF2 Proteins) as a critical molecular switch of PtdIns3K and autophagy activation, and its on/off state is precisely controlled by MTORC1 through phosphorylation.
Atg38 and its human ortholog NRBF2 (show NRBF2 Proteins), accessory components of complex I consisting of Vps15-Vps34-Vps30/Atg6 (show BECN1 Proteins)-Atg14 (yeast) and PIK3R4/VPS15-PIK3C3/VPS34-BECN1/Beclin 1 (show BECN1 Proteins)-ATG14 (human), were characterized.
p300 (show EP300 Proteins)-dependent VPS34 acetylation/deacetylation is the physiological key to VPS34 activation, which controls the initiation of canonical autophagy and of non-canonical autophagy in which the upstream kinases of VPS34 can be bypassed.
Low VPS34 expression is associated with cancer.
Arf tumor suppressor as a new transcriptional target of nuclear EGFR and highlight Vps34 as an important regulator of the nuclear EGFR/Arf survival pathway.
Vps34 has a previously unknown role in regulating Rab7 (show RAB7B Proteins) activity and late endosomal trafficking.
High expression of VPS34 promoted GRP78 (show HSPA5 Proteins) transcription by modulating ATF6 (show ATF6 Proteins). VPS34 could enhance GRP78 (show HSPA5 Proteins) protein stability.
These results establish Vps34 as an essential determinant of both short-term and long-term canonical GPCR signaling.
These results suggest that LEPR, MC4R, PIK3C3 and VRTN are useful markers for accurately predicting breeding values in Duroc pigs.
confirmed that the polymorphism in PIK3C3 (C2604T) has the potential to be a genetic marker for production traits in Duroc pigs
AP-1 (show JUN Proteins)/sigma1A (show AP1S1 Proteins)-ArfGAP1 (show ARFGAP3 Proteins)-Rabex-5 (show RABGEF1 Proteins) complex formation leads to more endosomal Rabex-5 (show RABGEF1 Proteins) and enhanced, Rab5 (show RAB5A Proteins)(GTP (show AK3 Proteins))-stimulated Vps34 PI3-kinase (show PIK3CA Proteins) activity, which is essential for multivesicular body endosome formation.
dendritic cells from Vps34-deficient mice have a partially activated phenotype, spontaneously produce cytokines, and exhibit enhanced activity of the classic MHC class I and class II antigen-presentation pathways and displayed a defect in the homeostatic maintenance of splenic CD8alpha(+) dendritic cells and in the capacity of these cells to cross-present cell corpse-associated antigens to MHC class I-restricted T cells.
Results demonstrate that Vps34 is essential for proper myelination by Schwann cells. Depletion of PI3P leads to enlarged late endosomal/lysosomal vacuoles and suppressed trafficking in Schwann cells. Suppressed endosomal trafficking likely causes changes in the abundance and post-translational modification of ErbB2 (show ERBB2 Proteins)/3, a signaling defect that may contribute to arrested myelination in Vps34 deficient nerves.
Phosphatidylinositol-3-phosphate is light-regulated, and Vps34 is essential for survival of retinal rod photoreceptor cells.
This study uncovers a dual role for Vps34 as a regulator of platelet production by megakaryocytes and as an unexpected regulator of platelet activation and arterial thrombus formation dynamics.
E. chaffeensis secretes Etf-1 (show ETF1 Proteins) to induce autophagy to repurpose the host cytoplasm and capture nutrients for its growth through RAB5 (show RAB5A Proteins) and class III PtdIns3K, while avoiding autolysosomal killing.
p300 (show NOTCH1 Proteins)-dependent VPS34 acetylation/deacetylation is the physiological key to VPS34 activation, which controls the initiation of canonical autophagy and of non-canonical autophagy in which the upstream kinases of VPS34 can be bypassed.
Vps34 has a previously unknown role in regulating Rab7 (show RAB7A Proteins) activity and late endosomal trafficking.
PIK3C3 was strongly expressed in the axon of cortical neurons during brain development.
Catalytic subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate which plays a key role in initiation and maturation of autophagosomes. Involved in the transport of lysosomal enzyme precursors to lysosomes. Required for the abcission step in cytokinesis (By similarity).
phosphoinositide-3-kinase, class 3
, phosphatidylinositol 3-kinase catalytic subunit type 3
, PI3K type 3
, PI3-kinase type 3
, ptdIns-3-kinase type 3
, phosphoinositide-3-kinase class 3
, catalytic phosphatidylinositol 3-kinase 3
, PtdIns-3-kinase type 3
, phosphatidylinositol 3-kinase p100 subunit
, class 3 phosphoinositide-3-kinase
, PI-3K Vps34p