PIK3CD

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Phosphoinositide 3-kinases (PI3Ks) phosphorylate inositol lipids and are involved in the immune response. The protein encoded by this gene is a class I PI3K found primarily in leukocytes. Like other class I PI3Ks (p110-alpha p110-beta, and p110-gamma), the encoded protein binds p85 adapter proteins and GTP-bound RAS. However, unlike the other class I PI3Ks, this protein phosphorylates itself, not p85 protein.[provided by RefSeq, Jul 2010]
Diseases associated with PIK3CD include Immunodeficiency 14A With Lymphoproliferation, Autosomal Dominant and Roifman-Chitayat Syndrome. Among its related pathways are IL-9 Signaling Pathways and Translation Insulin regulation of translation. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and kinase activity. An important paralog of this gene is PIK3CB.
Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides (PubMed:9235916).
Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396).
PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology.
Mediates immune responses.
Plays a role in B-cell development, proliferation, migration, and function.
Required for B-cell receptor (BCR) signaling.
Mediates B-cell proliferation response to anti-IgM, anti-CD40 and IL4 stimulation.
Promotes cytokine production in response to TLR4 and TLR9.
Required for antibody class switch mediated by TLR9.
Involved in the antigen presentation function of B-cells.
Involved in B-cell chemotaxis in response to CXCL13 and sphingosine 1-phosphate (S1P).
Required for proliferation, signaling and cytokine production of naive, effector and memory T-cells.
Required for T-cell receptor (TCR) signaling.
Mediates TCR signaling events at the immune synapse.
Activation by TCR leads to antigen-dependent memory T-cell migration and retention to antigenic tissues.
Together with PIK3CG participates in T-cell development.
Contributes to T-helper cell expansion and differentiation.
Required for T-cell migration mediated by homing receptors SELL/CD62L, CCR7 and S1PR1 and antigen dependent recruitment of T-cells.
Together with PIK3CG is involved in natural killer (NK) cell development and migration towards the sites of inflammation.
Participates in NK cell receptor activation.
Plays a role in NK cell maturation and cytokine production.
Together with PIK3CG is involved in neutrophil chemotaxis and extravasation.
Together with PIK3CG participates in neutrophil respiratory burst.
Plays important roles in mast-cell development and mast cell mediated allergic response.
Involved in stem cell factor (SCF)-mediated proliferation, adhesion and migration.
Required for allergen-IgE-induced degranulation and cytokine release.
The lipid kinase activity is required for its biological function.
Isoform 2 may be involved in stabilizing total RAS levels, resulting in increased ERK phosphorylation and increased PI3K activity.
Activated by growth factors and cytokine receptors through a tyrosine-kinase-dependent mechanism.
Activated by RAS.
IC87114 inhibits lipid kinase activity and is selective in cells at doses up to 5-10 uM.
IC87114 blocks T-cell receptor signaling in naive and memory T-cells and reduces cytokine production by memory T-cells.
phosphatidylinositol 3-kinase,catalytic,class 1,delta,subunit,expressed in leukocytes,binding p85 adaptor proteins (PIK3R1,PIK3R2,PIK3R3) and associating with activated receptor protein-tyrosine kinases,regulating cellular responses
Cytoplasm {ECO:0000269 PubMed:22020336}5
plasma membrane 5
Quaternary structure:
Heterodimer of a catalytic subunit PIK3CD and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3).
Interacts with ERAS (By similarity).
Interacts with HRAS.
Miscellaneous:
IC87114 inhibitor reduces passive cutaneous anaphylaxis, attenuates allergic airway inflammation and hyperresponsiveness and allergen induced rhinitis response.
Inhibitors may have therapeutic potential for the treatment of immune system-mediated diseases such as auto-immune diseases, inflammation and allergy (PubMed:17290298, 20940048).