After antigen receptor engagement, the membrane lipid phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2)
— which has a membrane-embedded lipid moiety and a cytoplasm-exposed
charged inositol phosphate (InsP) moiety — can either be converted into
PtdIns(3,4,5)P3 (referred to here as PtdInsP3) by phosphoinositide 3-kinases (PI3Ks) or into the second messengers diacylglycerol (DAG) and soluble Ins(1,4,5)P3 (referred to here as InsP3) by phospholipase Cγ1 (PLCγ1) or PLCγ2.
Phosphatase and tensin homologue (PTEN) counteracts PI3Ks.
SH2-domain-containing inositol-5-phosphatase 1 (SHIP1) and SHIP2 convert PtdInsP3 into PtdIns(3,4)P2. ( reaktio vain yhteen suuntaan).
Primarily through their InsP headgroups, PtdIns(4,5)P2, PtdInsP3 and PtdIns(3,4)P2 can bind to pleckstrin-homology (PH) domains in certain proteins and recruit them to membranes.
(Yleisesti tunnettua!) InsP3 mobilizes Ca2+ but can also be phosphorylated at position 3 to form Ins(1,3,4,5)P4 (referred to here as InsP4) by InsP3 3-kinases, including ITPKA, ITPKB, ITPKC and InsP multikinase (IPMK)11, 17, 18, 23, 34, 35.
Owing to its similarity to the PtdInsP3 headgroup, InsP4 can bind to the PH domains of certain PtdInsP3-binding proteins and
promote (in the case of IL-2-inducible T cell kinase (ITK) and tyrosine kinase expressed in hepatocellular carcinoma (TEC))
or inhibit (in the case of AKT and possibly Ras GTPase-activating protein 3 (RASA3)) the binding of these proteins to PtdInsP3.
In CD4+CD8+ thymocytes, InsP4-mediated promotion of PtdInsP3 binding to the ITK and/or TEC PH domains establishes a feedback loop of PLCγ1 activation.
In neutrophils, InsP4-mediated inhibition of the binding of PtdInsP3 or PtdIns(3,4)P2 to the PH domain of AKT may limit the membrane recruitment of AKT.
InsP4 can also inhibit RASA3 binding to PtdIns(4,5)P2 or PtdInsP3 (Refs 18, 21). Whether this occurs in leukocytes is unknown. Red boxes denote enzymes with demonstrated physiological relevance in leukocytes. R, fatty-acid side chain.
Phosphatase and tensin homologue (PTEN) counteracts PI3Ks.
SH2-domain-containing inositol-5-phosphatase 1 (SHIP1) and SHIP2 convert PtdInsP3 into PtdIns(3,4)P2. ( reaktio vain yhteen suuntaan).
Primarily through their InsP headgroups, PtdIns(4,5)P2, PtdInsP3 and PtdIns(3,4)P2 can bind to pleckstrin-homology (PH) domains in certain proteins and recruit them to membranes.
(Yleisesti tunnettua!) InsP3 mobilizes Ca2+ but can also be phosphorylated at position 3 to form Ins(1,3,4,5)P4 (referred to here as InsP4) by InsP3 3-kinases, including ITPKA, ITPKB, ITPKC and InsP multikinase (IPMK)11, 17, 18, 23, 34, 35.
Owing to its similarity to the PtdInsP3 headgroup, InsP4 can bind to the PH domains of certain PtdInsP3-binding proteins and
promote (in the case of IL-2-inducible T cell kinase (ITK) and tyrosine kinase expressed in hepatocellular carcinoma (TEC))
or inhibit (in the case of AKT and possibly Ras GTPase-activating protein 3 (RASA3)) the binding of these proteins to PtdInsP3.
In CD4+CD8+ thymocytes, InsP4-mediated promotion of PtdInsP3 binding to the ITK and/or TEC PH domains establishes a feedback loop of PLCγ1 activation.
In neutrophils, InsP4-mediated inhibition of the binding of PtdInsP3 or PtdIns(3,4)P2 to the PH domain of AKT may limit the membrane recruitment of AKT.
InsP4 can also inhibit RASA3 binding to PtdIns(4,5)P2 or PtdInsP3 (Refs 18, 21). Whether this occurs in leukocytes is unknown. Red boxes denote enzymes with demonstrated physiological relevance in leukocytes. R, fatty-acid side chain.
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