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Literature summary for 2.7.1.153 extracted from

  • Marwick, J.A.; Chung, K.F.; Adcock, I.M.
    Phosphatidylinositol 3-kinase isoforms as targets in respiratory disease (2010), Ther. Adv. Respir. Dis., 2009, 1-16.
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
additional information class IA are activated by cell surface expressed receptor tyrosine kinases, such as growth factors, insulin and cytokines, while class IB are activated by G-protein coupled receptors. The single class 1B catalytic isoform p110gamma binds to either p101 or p84/p87 adaptors, which function to potentiate activation by betagamma-subunits of heterotrimeric GTP-binding proteins which facilitate intracellular signalling from G-protein coupled receptors Mus musculus
additional information class IA are activated by cell surface expressed receptor tyrosine kinases, such as growth factors, insulin and cytokines, while class IB are activated by G-protein coupled receptors. The single class 1B catalytic isoform p110gamma binds to either p101 or p84/p87 adaptors, which function to potentiate activation by betagamma-subunits of heterotrimeric GTP-binding proteins which facilitate intracellular signalling from G-protein coupled receptors Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information genetic abolition of PI3Kdelta signalling by insertion of a kinase-dead p110delta catalytic subunit results in impaired B cell and T cell antigen receptor signalling Homo sapiens
additional information mutations in catalytic subunit PI3Kdelta, PI3KdD910/A910 mice display impaired B cell development and differentiation including a reduction in B cell progenitor cells and an increase in the ratio of pre-(CD43-IgM+) to pro-(CD43+ IgM-) B cells. T cell differentiation into Th1, Th2 and Treg lineages are also impaired in PI3KdD910/A910 mice by a mechanism involving reduced T cell receptor activation of Akt and FOXO Mus musculus

Inhibitors

Inhibitors Comment Organism Structure
IC87114 a selective PI3Kdelta inhibitor Homo sapiens
LY294002
-
Homo sapiens
additional information pan-PI3K inhibition and inhibition of only PI3Kdelta results in attenuated vascular leakage, tissue eosinophilia, airway mucus production, and AHR as well as release of cytokines, chemokines and adhesion molecules Homo sapiens
Wortmannin
-
Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate Mus musculus
-
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate Homo sapiens
-
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Mus musculus
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
heart PI3Kgamma, small amounts Mus musculus
-
heart PI3Kgamma, small amounts Homo sapiens
-
leukocyte PI3Kdelta is absolutely restricted to, and PI3Kgamma is largely restricted to leukocytes Mus musculus
-
leukocyte PI3Kdelta is absolutely restricted to, and PI3Kgamma is largely restricted to leukocytes Homo sapiens
-
additional information PI3Kalpha and beta are ubiquitously expressed while the expression of PI3Kdelta is restricted to leukocytes Mus musculus
-
additional information PI3Kalpha and beta are ubiquitously expressed while the expression of PI3Kdelta is restricted to leukocytes Homo sapiens
-
uterine endometrium PI3Kgamma, small amounts Mus musculus
-
uterine endometrium PI3Kgamma, small amounts Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
-
Mus musculus ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
-
Homo sapiens ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
?
additional information the single class 1B catalytic isoform p110gamma binds to either p101 or p84/p87 adaptors, which function to potentiate activation by betagamma-subunits of heterotrimeric GTP-binding proteins which facilitate intracellular signalling from G-protein coupled receptors Mus musculus ?
-
?
additional information the single class 1B catalytic isoform p110gamma binds to either p101 or p84/p87 adaptors, which function to potentiate activation by betagamma-subunits of heterotrimeric GTP-binding proteins which facilitate intracellular signalling from G-protein coupled receptors Homo sapiens ?
-
?

Subunits

Subunits Comment Organism
heterodimer the catalytic subunits of the class IA PI3Ks form heterodimers with one of five Src-homology 2, SH2, domain-containing regulatory subunits p85alpha, p85beta, p55alpha, p55gamma and p50alpha, which bind with high affinity to phosphorylated tyrosines of receptor tyrosine kinases Mus musculus
heterodimer the catalytic subunits of the class IA PI3Ks form heterodimers with one of five Src-homology 2, SH2, domain-containing regulatory subunits p85alpha, p85beta, p55alpha, p55gamma and p50alpha, which bind with high affinity to phosphorylated tyrosines of receptor tyrosine kinases Homo sapiens

Synonyms

Synonyms Comment Organism
class I PI3K
-
Mus musculus
class I PI3K
-
Homo sapiens
More class I PI3Ks can be further subtyped depending on their associated catalytic subunit into class IA p110alpha, p110beta and p110delta and class IB p110gamma Mus musculus
More class I PI3Ks can be further subtyped depending on their associated catalytic subunit into class IA p110alpha, p110beta and p110delta and class IB p110gamma Homo sapiens

Cofactor

Cofactor Comment Organism Structure
ATP
-
Mus musculus
ATP
-
Homo sapiens

Expression

Organism Comment Expression
Mus musculus upregulation of class I PI3K isozymes in cancer cells up
Homo sapiens upregulation of class I PI3K isozymes in cancer cells up

General Information

General Information Comment Organism
malfunction individual class I PI3K isoforms are strongly linked with the regulation of oncogenes and tumorigenesis. PI3Ka is upregulated and/or mutated in a variety of carcinomas, and in particular lung tumours, and is associated with an elevation in activation and signalling of the serine-threonine kinase Akt, overview Mus musculus
malfunction PI3K signalling is involved in development of respiratory diseases, such as asthma and cystic fibrosis, and lung cancer, detailed overview. Inhibition of PI3Kdelta and gamma may provide a beneficial therapeutic strategy for the reduction of Th1/Th2 and Tc1 cells in respiratory disease. Individual class I PI3K isoforms are strongly linked with the regulation of oncogenes and tumorigenesis. PI3Ka is upregulated and/or mutated in a variety of carcinomas, and in particular lung tumours, and is associated with an elevation in activation and signalling of the serine-threonine kinase Akt, overview Homo sapiens
physiological function the signalling pathways regulated by class 1 PI3K signalling are central in many of the fundamental cellular processes associated with PI3K signalling including cell growth, proliferation, migration and survival, signaling pathway overview Mus musculus
physiological function the signalling pathways regulated by class 1 PI3K signalling are central in many of the fundamental cellular processes associated with PI3K signalling including cell growth, proliferation, migration and survival, signaling pathway overview Homo sapiens