Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta(PIK3CD) phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta(PIK3CD) Related Genes Homo sapiens
CYTOBAND 1p36.2,
GENERIF_SUMMARY PI3K delta can play a selective role in the amplification of phosphatidylinositol (3,4,5) trisphosphate (PIP3) levels that lead to neutrophil polarization and regulate directional migration, but not random locomotion., p110delta isoform of PI3K is consistently expressed at a high level in blast cells from AML, in contrast to the other class I isoforms, Stimulation of TNF-alpha-primed human neutrophils with fMLP results in biphasic activation of PI3K; the first phase is largely dependent on PI3Kgamma; the second phase is largely dependent on PI3Kdelta and regulates parallel activation of ROS production, p110beta, -gamma, and -delta isoforms of class I phosphoinositide 3-kinase have roles in oncogenic transformation, These findings could shed light on further understanding the polymorphisms of p110delta in B-cell immunodeficiency and different populations., p110delta contributes significantly to Th cell expansion and differentiation in vitro and in vivo, also in the context of CD28 costimulation., This review describes the second-messenger PI3K delta signalling pathways that are involved in immune responses relevant to the pathogenesis of rheumatoid arthritis and other inflammatory diseases., identifies the RhoA/ROCK pathway as a major target of p110delta-mediated PI3K signalling, novel function of the class I(A) PI3K isoform p110delta in neuroblastoma growth and survival., These results demonstrate that CD148 may interact with and dephosphorylate p85 when it is phosphorylated and modulate the magnitude of phosphoinositide 3-kinase activity., In contrast with PI3Kalpha, beta and gamma, PI3Kdelta accounts for most of the PI3K-dependent signaling ruling the production of IL-1beta, IL-6, TNF and sIL-1Ra in monocytes., Results identify a conserved phosphoinositide 3-kinase p11delta promoter region that may account for the predominant leukocyte expression of p110delta., RUNX1 may play a critical role in chemotherapy response in acute megakaryocytic leukemia by regulating the PI3-kinase/Akt pathway., These studies establish that previously activated memory T cells are at least as sensitive to p110delta inhibition as naive T cells and show that mouse models accurately predict p110delta function in human T cells., Data show that similar responses were seen in cancer cells with wild-type or activated mutant PI3K genes treated with p110alpha/delta or p110alpha/beta/delta inhibitors in cell viability assays., PI3Kdelta expression and signaling is increased in the lungs of patients with COPD., IFN-beta triggers an atypical MEK2/PI3Kdelta signaling cascade to regulate sIL-1Ra expression in monocytes., These observations suggest that PI3Kdelta contributes to induction of enhanced systemic lupus erythematosus memory T cell survival, PI3K p110delta is important for TGFB1 induced production of the contractile proteins calponin and alpha-SMA and the proinflammatory cytokine IL-6, p37delta appears to be a new tumor-specific isoform of p110delta with growth-promoting properties, Isoform specific targeting of PI3Kdelta may be beneficial in the treatment of glioblastoma multiforme by specifically inhibiting tumour cell migration capacity., p110delta-dependent translocation of exogenous CSF-1 to the nucleus-associated CSF-1Rs, correlating with a prominent role of p110delta in activation of the Rab5 GTPase, a key regulator of endocytic trafficking, Findings suggest that excessive PI3Kdelta activity is characteristic in Hodgkin lymphoma (HL) and support clinical evaluation of GS-1101, alone and in combination, as targeted therapy for HL., present a detailed biochemical and bioinformatic characterization of p110delta gene regulation, demonstrating that PIK3CD has distinct promoters, some of which can be dynamically activated by pro-inflammatory mediators, PI3 kinase delta is a key regulator of synoviocyte function in rheumatoid arthritis., PIK3CD shows evidence of association with schizophrenia, and is a previously undescribed therapeutic target for the treatment of psychiatric disorders., Studies indicate that the research with phosphoinositide 3-kinase p110-delta (p110delta) in chronic lymphocytic leukemia (CLL) have led to a more fundamental understanding of CLL signaling defects., High PIK3CA/PIK3CD ratio identified a subset of primary mantle cell lymphomas resistant to GS-1101 and this ratio increased significantly with relapse., The expression of PIK3CD is inversely correlated with miR-30a levels in metastatic colorectal carcinoma tissues., These results suggest that PI3Kdelta mediates dsRNA-induced upregulation of B7-H1 without affecting the activation of NF-kappaB., this study found E1021K in 17 patients with activated PI3K-delta syndrome (APDS), from seven unrelated families with, but not among 3346 healthy subjects., Data indicate that patients with combined immunodeficiency disease who share gain-of-function mutations in PIK3CD (p110delta), resulting in hyperactivation of mTOR signaling and skewed the differentiation of CD8+ T cells., Study reveals functional and mechanistic links between miRNA-30b and oncogene KRAS, PIK3CD and BCL2 in the pathogenesis of colorectal carcinoma., PI3Kdelta contributes to multiple aspects of the pathogenic FLS behavior in RA. These observations, together with previous findings that PI3Kdelta regulates FLS growth and survival, PIK3CD is a target gene of miR-125b in Ewing's sarcoma cells. RT-PCR and western blot assays identify over-expression of miR-125b that suppresses the expression of PIK3CD mRNA and protein., PIK3CD was inversely correlated with miR-663 in glioblastoma specimens and predicted poor prognosis of patients with glioblastoma, Gestational diabetes mellitus is accompanied by leukocyte PIK3CD overexpression associated with reduced plasma LDL-C and TC levels, as well as with hyperglycaemia and elevated leukocyte SIRT1 mRNA., PI3K p110delta uniquely promotes gain-of-function Shp2-induced GM-CSF hypersensitivity in a model of juvenile myelomonocytic leukemia., Mutations in PIK3CD can cause hyper IgM syndrome (HIGM) associated with increased cancer susceptibility., The p110delta PI3K-selective compound CAL-101 (Idelalisib) did not inhibit markers of PI3K activity in cancer or stromal cells., Patients with activated phosphoinositide 3-kinase delta syndrome (mutation in PIK3CD) develop B-cell lymphomas., These results collectively indicate that inducible PI3Kdelta plays a crucial role in persistent activation of PI3K-Akt in fibroblast-like synoviocytes, and in the formation of a hypertrophic synovial lining., Data indicate a series of quinolinylpurines as potent and selective PI3Kdelta kinase inhibitors with in vivo efficacy as measured by two rodent disease models of inflammation and autoimmune disease., Expression of functional S1PR1 is reduced by B cell receptor signaling and increased by inhibition of PIK3CD but not SYK or BTK in chronic lymphocytic leukemia cells., work identifies FAK as a target of p110delta PI3K that links RhoA with PTEN and establishes for the first time that PTEN is a substrate of FAK-mediated Tyr phosphorylation, Combined PI3K/Akt and Hsp90 targeting synergistically suppresses essential functions of alloreactive T cells and increases Tregs., Studies indicate that phosphatidylinositol-45-bisphosphate 3-kinase 110 kDa catalytic subunit (PIK3CD p110delta) have been described (N334K, C416R, E525K and E1021K with the majority of cases carrying E1021K) as a cause for primary immunodeficiency., study concludes that activating mutations in PIK3CD may cause immunodeficiency in patients with a complex phenotype combining defective B and T cell responses, but are less likely to be discovered in patients where only the humoral arm of the immune response is affected and naive T cell numbers are normal, Impaired signaling and protein synthesis through the PI3K catalytic subunit p110delta is an underlying molecular defect and potential treatment target in select autism spectrum disorders.,
OMIM_DISEASE Immunodeficiency 14,
SP_COMMENT catalytic activity:ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate., pathway:Phospholipid metabolism; phosphatidylinositol phosphate biosynthesis., PTM:Autophosphorylation on Ser-1039 results in the almost complete inactivation of the lipid kinase activity., similarity:Belongs to the PI3/PI4-kinase family., similarity:Contains 1 PI3K/PI4K domain., subunit:Heterodimer of a p110 (catalytic) and a p85 (regulatory) subunit. Interacts with ERAS., tissue specificity:Expressed predominantly in leukocytes.,