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 | 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 | 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 | 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 | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Mus musculus | - |
- |
- |
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 | 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 | 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 | 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 | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Mus musculus | |
ATP | - |
Homo sapiens |
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 | 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 |