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Literature summary for 2.7.11.1 extracted from

  • Thomas, D.; Powell, J.A.; Green, B.D.; Barry, E.F.; Ma, Y.; Woodcock, J.; Fitter, S.; Zannettino, A.C.; Pitson, S.M.; Hughes, T.P.; Lopez, A.F.; Shepherd, P.R.; Wei, A.H.; Ekert, P.G.; Guthridge, M.A.
    Protein kinase activity of phosphoinositide 3-kinase regulates cytokine-dependent cell survival (2013), PLoS Biol., 11, e1001515.
    View publication on PubMedView publication on EuropePMC

Activating Compound

Activating Compound Comment Organism Structure
cytokine physiological concentrations of cytokine in the picomolar range were sufficient for activating the protein kinase activity of PI3K leading to Ser585 phosphorylation and hemopoietic cell survival but did not activate PI3K lipid kinase signaling or promote proliferation Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information overexpression of the GFP-tagged PH domain of Akt1 blocks the binding of endogenous PH-domain proteins (such as Akt) to phosphatidyl inositol phosphates in the plasma membrane thereby abrogating PI3K lipid signaling but permitting PI3K protein kinase signaling. The inducible expression of a mutant form of PI3K that is defective in lipid kinase activity but retains protein kinase activity is able to promote Ser585 phosphorylation and hemopoietic cell survival in the absence of cytokine. Blockade of p110alpha by RNA interference or multiple independent PI3K inhibitors not only blocks Ser585 phosphorylation in cytokine-dependent cells and primary human AML blasts, but also results in a block in survival signaling and cell death Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
Ctl peptide
-
Homo sapiens
LY294002
-
Homo sapiens
additional information expression of the pleckstrin homology of Akt1 has no significant impact on the ability of picomolar concentrations of cytokine to promote hemopoietic cell survival Homo sapiens
PIK-75 a p110alpha-selective PI3K inhibitor Homo sapiens
SB203580 slight inhibition of the protein kinase Homo sapiens
YM024 a p110alpha-selective PI3K inhibitor Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + granulocyte macrophage colony stimulating factor receptor Homo sapiens
-
ADP + phospho-granulocyte macrophage colony stimulating factor receptor
-
?
ATP + interleukin 3 Homo sapiens
-
ADP + phospho-interleukin-3
-
?
additional information Homo sapiens phosphoinositide 3-kinase (PI3K) is a dual specificity kinase that is able to phosphorylate both lipid and protein substrates. In addition to their lipid kinase activity, all members of the class 1 PI3K family also possess intrinsic protein kinase activity ?
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P42336 isozyme PI3Kalpha
-

Source Tissue

Source Tissue Comment Organism Textmining
leukemia cell primary human acute myeloid leukemia (AML) cells Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + granulocyte macrophage colony stimulating factor receptor
-
Homo sapiens ADP + phospho-granulocyte macrophage colony stimulating factor receptor
-
?
ATP + granulocyte macrophage colony stimulating factor receptor Ser585 phosphorylation in the cytoplasmic domain Homo sapiens ADP + phospho-granulocyte macrophage colony stimulating factor receptor
-
?
ATP + interleukin 3
-
Homo sapiens ADP + phospho-interleukin-3
-
?
ATP + interleukin 3 Ser585 phosphorylation in the cytoplasmic domain Homo sapiens ADP + phospho-interleukin-3
-
?
additional information phosphoinositide 3-kinase (PI3K) is a dual specificity kinase that is able to phosphorylate both lipid and protein substrates. In addition to their lipid kinase activity, all members of the class 1 PI3K family also possess intrinsic protein kinase activity Homo sapiens ?
-
?
additional information the p110alpha catalytic subunit of PI3K can directly phosphorylate Ser585 of the GM-CSF and IL-3 receptors Homo sapiens ?
-
?

Synonyms

Synonyms Comment Organism
p110alpha
-
Homo sapiens
phosphoinositide 3-kinase
-
Homo sapiens
PI3K
-
Homo sapiens

Cofactor

Cofactor Comment Organism Structure
ATP
-
Homo sapiens

General Information

General Information Comment Organism
malfunction Blockade of p110alpha by RNA interference or multiple independent PI3K inhibitors not only blocks Ser585 phosphorylation in cytokine-dependent cells and primary human AML blasts, but also results in a block in survival signaling and cell death Homo sapiens
physiological function phosphoinositide 3-kinase (PI3K) is a dual specificity kinase that is known to be involved in cell survival and malignant transformation, and it is able to phosphorylate both lipid and protein substrates. PI3K protein kinase activity can directly phosphorylate growth factor receptors on human hematopoietic (blood) cells to promote a survival-only response. The protein kinase activity but not the lipid kinase activity of PI3K promotes cytokine-mediated cell survival. It phosphorylates serine residues in the cytoplasmic portion of cytokine receptors to promote hemopoietic cell survival. The PI3K lipid kinase activity is not essential for regulating cell survival Homo sapiens