2.7.1.153: phosphatidylinositol-4,5-bisphosphate 3-kinase
This is an abbreviated version!
For detailed information about phosphatidylinositol-4,5-bisphosphate 3-kinase, go to the full flat file.
Word Map on EC 2.7.1.153
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2.7.1.153
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wortmannin
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pten
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mapks
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mtor
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rapamycin
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endothelial
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erk
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colorectal
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signal-regulated
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subtypes
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insulin-like
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pkc
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tumour
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adenocarcinoma
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phospholipase
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akt1
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insulin-stimulated
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irs-1
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erbb2
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mitogen
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adipocytes
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integrins
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tensin
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insulin-induced
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3-kinases
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dominant-negative
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platelet-derived
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hotspot
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pi3k-akt
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progression-free
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substrate-1
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igf-i
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sh2
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ctnnb1
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tyrosine-phosphorylated
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phosphatidylinositol-3
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pleckstrin
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cdkn2a
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rac1
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pi3k-dependent
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her2-negative
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cetuximab
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phosphatidylinositol-3-kinase
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everolimus
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anti-egfr
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pdgfra
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trastuzumab
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her2-positive
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phospho-akt
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endometrioid
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medicine
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pharmacology
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analysis
- 2.7.1.153
- wortmannin
- pten
- mapks
- mtor
- rapamycin
- endothelial
- erk
- colorectal
-
signal-regulated
- subtypes
-
insulin-like
- pkc
- tumour
- adenocarcinoma
- phospholipase
- akt1
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insulin-stimulated
- irs-1
- erbb2
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mitogen
- adipocytes
- integrins
-
tensin
-
insulin-induced
- 3-kinases
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dominant-negative
-
platelet-derived
-
hotspot
-
pi3k-akt
-
progression-free
- substrate-1
- igf-i
- sh2
-
ctnnb1
-
tyrosine-phosphorylated
-
phosphatidylinositol-3
-
pleckstrin
-
cdkn2a
- rac1
-
pi3k-dependent
-
her2-negative
- cetuximab
-
phosphatidylinositol-3-kinase
-
everolimus
-
anti-egfr
-
pdgfra
- trastuzumab
-
her2-positive
-
phospho-akt
-
endometrioid
- medicine
- pharmacology
- analysis
Reaction
Synonyms
class I phosphoinositide 3-kinase, class I PI3K, class IA phosphatidylinositol 3-kinase, class IA phosphatidylinositol-4,5-bisphosphate 3-kinase, CXCR2/phosphatidylinositol 3-kinase gamma, kinase (phosphorylating), phosphatidylinositol 4,5-diphosphate 3-, More, p101-PI3K, p110alpha, p110beta, p110delta, p110delta PI 3-kinase, p110gamma/p101, P120-PI3K, phosphatidyl-inositol-3-kinase, phosphatidylinositol (4,5)-bisphosphate 3-hydroxykinase, phosphatidylinositol 3'-kinase, phosphatidylinositol 3-hydroxyl kinase, phosphatidylinositol 3-kinase alpha, phosphatidylinositol 3-kinase gamma, phosphatidylinositol-4,5-bisphosphate 3-kinase, phosphoinositide 3-kinase, phosphoinositide 3-kinase p110delta, phosphoinositol 3-kinase, PI 3-K, PI 3-kinase, PI-3K, PI3-K, PI3-kinase, PI3K, PI3K p110delta, PI3Kalpha, PI3Kbeta, PI3Kdelta, PI3Kgamma, PI3Kp110delta, PIK3, PIK3CA, Pik3r1, PtdIns(4,5)P2 3-OH kinase, PtdIns-3-kinase p101, PtdIns-3-kinase p110, PtdInsP 3-OH-kinase, type I phosphoinositide 3-kinase
ECTree
2.7.1.153 phosphatidylinositol-4,5-bisphosphate 3-kinaseAdvanced search results
results (
results (Engineering
Engineering on EC 2.7.1.153 - phosphatidylinositol-4,5-bisphosphate 3-kinase
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
M582V
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site-directed mutagenesis, the full-length p85alpha isoform inter-SH2 domain mutation enables the mutant PI3K to bind influenza A virus NS1 protein leading to activation of the mutant PI3K enzyme activity, molecular modeling, overview
V573M
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site-directed mutagenesis, the p85beta isoform inter-SH2 domain mutation abrogates mutant PI3K binding to influenza A virus NS1 protein, molecular modeling, overview
D1017H
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a common naturally occuring somatic mutation involved in cancer development
E542K
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a common naturally occuring mutation in the helical domain, the mutation is involved in cancer development, the mutant requires RAS binding but bot p85 binding
E542K/E545K
E545K
E545K/H1047R
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gain-of-function helical domain mutations result in upregulation of enzyme activity, Akt phosphorylation and cell transformation
H1047R
M1043I
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a common naturally occuring somatic mutation involved in cancer development
M326I
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a common naturally occuring polymorphism of the regulatory subunit p85alpha in women involved in the polycystic ovary syndrome, PCOS, genotyping in polycystic ovary syndrome patients from Korean female population
N345K
P124L
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a common naturally occuring somatic mutation involved in cancer development. P124L lies in a region of four helices in the protein between the adapter-binding and RAS-binding domains
P124T
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a naturally occuring missense mutation in codon 124 from a colorectal cancer cell
Q643R
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a common naturally occuring somatic mutation involved in cancer development
R274A
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the GTPase-activating protein activity toward Rab5 and Rab4 of PI3K p85alpha subunit is abolished in the mutant. Expression of p85alpha-R274A results in increased platelet-derived growth factor receptor, PDGFR, activation and downstream signaling, via Akt and MAPK pathways, and in decreased PDGFR degradation. Disrupted RabGAP function of the p85 subunit of phosphatidylinositol 3-kinase results in cell transformation, co-expression of a dominant negative Rab5-S34N mutant attenuates these transformed properties
R38C/R88C
the mutation significantly change the distance distribution for helical domain residues K379, I381 and K382
D910A
M582V
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site-directed mutagenesis, the full-length p85alpha isoform inter-SH2 domain mutation enables the mutant PI3K to bind influenza A virus NS1 protein leading to activation of the mutant PI3K enzyme activity, molecular modeling, overview
V573M
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site-directed mutagenesis, the p85beta isoform inter-SH2 domain mutation abrogates mutant PI3K binding to influenza A virus NS1 protein, molecular modeling, overview
additional information
E542K/E545K
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gain-of-function helical domain mutations result in upregulation of enzyme activity, Akt phosphorylation and cell transformation
E542K/E545K
the mutation disrupts the interaction between residues E545 (helical domain) and K379 (nSH2 domain)
E545K
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a common naturally occuring mutation in the helical domain, the mutation is involved in cancer development, the mutant requires RAS binding but bot p85 binding
E545K
site-directed mutagenesis of p110alpha, an oncogenic mutant enzyme form
H1047R
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a common naturally occuring mutation of the kinase domain, that is involved in cancer development
H1047R
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gain-of-function mutation of subunit p110alpha, the H1047R mutation can substitute for RAS binding, but binding to p85 is essential for H1047R-induced cell transformation
H1047R
site-directed mutagenesis of p110alpha, an oncogenic mutant enzyme form
N345K
the mutation significantly change the distance distribution for helical domain residues K379, I381 and K382
N345K
a naturally occuring oncogenic p110alpha mutant
D910A
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site-directed mutagenesis of isoform p110delta, catalytically inactive. Interleukin is unable to induce hyper-responsiveness in tissues expressing the mutant
D910A
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mice with an inactivating knock-in mutation in the p110delta isoform of PI3K, p110deltaD910A, generated on Leishmanina major resistant and susceptible genetic backgrounds. The mutant mice show severely impaired T cell responses, but the mutant mice also show more robust resistance to Leishmanina major infection manifested as significantly reduced lesion size and accelerated parasite clearance. Cells from p110D910A mice were significantly impaired in their ability to make cytokines, particularly IFN-gamma, interleukin-10, and TNF, phenotypes, overview
additional information
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construction of chimeras of 85alpha and p85beta iSH2 domain by overlapping PCR using mouse p85beta and bovine p85alpha as templates
additional information
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a mutant with a deletion in the binding site of the p110 catalytic subunit is dominant negative
additional information
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a mutant with a deletion in the binding site of the p110 catalytic subunit is dominant negative
additional information
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construction of a constitutively active PI3-kinase, CA-PI3K, mutant, whose expression stimulates translocation of Tiam1 to the membrane, increases Rac1 activity, and increases wound healing of airway epithelial cells, phenotype, overview. Expression of a dominant negative form of PI3-kinase,using an adenoviral vector, causes inhibition of airway epithelial cell wound closure, overview
additional information
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construction of a dominant negative PI3K mutant by PCR cloning. Legionella pneumophila entry into macrophages expressing the mutant is reduced
additional information
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deficiency of PI3-K regulatory subunit p85alpha in vivo results in a significantly greater number of trabeculae and significantly lower spacing between trabeculae as well as increased bone mass in both males and females compared to their sex-matched wild-type controls. p85-/- osteoclast progenitors show impaired growth and differentiation, which is associated with reduced activation of Akt and mitogen-activated protein kinase Erk1/Erk2 in vitro, and a significant reduction in the ability of p85-/- osteoclasts to adhere to as well as to migrate via integrin alphanybeta3. Restoring the expression of the full-length form of p85alpha but not the version with a deletion of the Src homology-3 domain restores the maturation of p85-/- osteoclasts to wild-type levels, overview. Phenotypes, overview
additional information
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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
additional information
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helical domain and kinase domain mutations in p110alpha of phosphatidylinositol 3-kinase induce gain of function by different mechanisms, overview. About 30% of prostate, breast, cervix, and endometrium tumors show catalytic subunit p110alpha mutations, the most prominent single amino acid substitutions in the helical or kinase domain result in a gain of enzymatic function, activate AKT signaling, and induce oncogenic transformation, analysis of hot-spot mutations in gene PIK3CA. The gain of function induced by helical domain mutations is independent of binding to p85 but requires interaction with RAS-GTP. In contrast, the kinase domain mutation is active in the absence of RAS-GTP binding but is highly dependent on the interaction with p85. Truncation reduce the activities of all enzymes, truncated wild-type and mutant, overview. Phenotypes, overview
additional information
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mutations in PIK3CA are also found commonly in the benign skin lesions seborrheic keratosis and epidermal nevi
additional information
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sequencing of cancer cell p85alpha subunits reveal four mutational alterations, three colonic and one ovarian: one with an early stop codon after Asp605 and three containing small in-frame deletions, DELTALeu570-Gln572, DELTALeu570-Asp578, and DELTAMet582-Asp605. These deletions are located near the negative regulatory phosphorylation site Ser608 within p85alpha. All mutations lead to increased enzyme activity
additional information
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suppression of the PI3K catalytic subunit p110alpha inhibits the growth of ovarian cancer cells in vitro and in vivo
additional information
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the most common sites for hotspot mutations of PI3Kalpha are around amino acid 1047 in the kinase domain, and amino acid 545 in the helical domain, the mutations are involved in breast and colon tumorigenesis
additional information
determination of p110alpha subunit oncogenic mutations disrupt the interactions at the p110alpha-p85alpha interface, overview. Even distant mutations (R38C/R88Q and N345K) effectively weaken the interaction between the nSH2 and helical domain, thus increasing the population of molecules that are not inhibited by the the nSH2 domain. The oncogenic mutations increase the conformational heterogeneity of the p85alpha subunit and lead to PI3Kalpha activation by releasing the p85? nSH2 inhibitory effect
additional information
N-terminal tags on the catalytic (p110) subunit of phosphoinositol 3-kinase increase cell signalling and oncogenic transformation
additional information
N-terminal tags on the catalytic (p110) subunit of phosphoinositol 3-kinase increase cell signalling and oncogenic transformation
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
additional information
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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
additional information
p110 subunit knockdown via specific siRNA application
additional information
p110 subunit knockdown via specific siRNA application
additional information
p110 subunit knockdown via specific siRNA application
additional information
knockdown of PIK3CA/p110alpha in a panel of glioblastoma cell lines
additional information
somatic gain of function PIK3CA-mutation due to a pathogenic heterozygous missense mutation in PIK3CA, phenotype, overview
additional information
expression of regulatory protein p85 102 amino acid binding domain plus catalytic subunit p110 leads to fully active enzyme complex
additional information
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expression of regulatory protein p85 102 amino acid binding domain plus catalytic subunit p110 leads to fully active enzyme complex
additional information
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heterozygous disruption of p85alpha regulatory subunit, increase in enzyme activity and decrease in apoptosis by insulin-like growth factor 1 through upregulated phosphatidylinositol (3,4,5)-triphosphate production. Complete depletion of regulatory subunit p85alpha results in significantly increased apoptosis due to reduced enzyme-dependent signaling
additional information
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genetic deletion or selective inhibition of isoform PI3Kdelta diminishes joint erosion to a level comparable to its PI3Kgamma counterpart. The induction and progression of joint destruction is profoundly reduced in the absence of both PI3K isoforms and correlates with a limited ability of neutrophils to migrate into tissue in response to leukotriene B4. fMLP-induced neutrophil extravasation is primarily reliant on PI3Kgamma
additional information
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construction of chimeras of 85alpha and p85beta iSH2 domain by overlapping PCR using mouse p85beta and bovine p85alpha as templates
additional information
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generation of different transgenic lines expressing myristoylated p110A protein under the control of the epithelial-specific mouse mammary tumor virus promoter, i.e. myrp110A transgenic mice. The membrane localization of p110alpha predisposes mammary glands to neoplastic transformation, young female mutant mice show delayed mammary gland involution and morphologic changes of the mammary ducts, which is more pronounced in old animals, especially in mutiparous females, in which increased ductal branching, alveolar hyperplasia, and intraductal neoplasia are observed, phenotype, overview
additional information
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generation of p110gamma knockout mice. p110gamma-deficient effector CD8 T cells exhibit impaired migration in vitro and exhibit reduced migration into the inflamed peritoneum following vaccinia virus challenge in vivo. Furthermore, p110gamma-/- mice exhibit reduced influx in response to virus-induced peritonitis and exhibit increased susceptibility to vaccinia virus infection when compared with wild-type mice, phenotype, overview
additional information
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mRNA translation of IFN-responsive genes is defective in cells with targeted disruption of both the p85alpha and p85beta subunits of PI3K
additional information
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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
additional information
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p110-/- CD4 lymphocytes are phenotypically identical to their wild-type counterparts and do not exhibit any defects in TCR-mediated calcium mobilization or Erk activation. p110gamma-deficient CD4 OT.II T cells become activated and proliferate comparably with WT cells in response to antigen in vivo. But antigen-experienced p110gamma-deficient CD4 OT.II lymphocytes exhibit dramatic defects in their ability to traffic to peripheral inflammatory sites in vivo and exhibit impaired F-actin polarization and migration in response to stimulation ex vivo with the CCR4 ligand CCL22
additional information
generation of a mouse model of smooth muscle cellspecific p110alpha deficiency. Targeted deletion of p110alpha in sm-p110alpha-/- mice blunts growth factorinduced cellular responses and abolishes neointima formation after balloon injury of the carotid artery in mice. p110 Subunit knockdown via specific siRNA application
additional information
generation of a mouse model of smooth muscle cellspecific p110alpha deficiency. Targeted deletion of p110alpha in sm-p110alpha-/- mice blunts growth factorinduced cellular responses and abolishes neointima formation after balloon injury of the carotid artery in mice. p110 Subunit knockdown via specific siRNA application
additional information
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generation of a mouse model of smooth muscle cellspecific p110alpha deficiency. Targeted deletion of p110alpha in sm-p110alpha-/- mice blunts growth factorinduced cellular responses and abolishes neointima formation after balloon injury of the carotid artery in mice. p110 Subunit knockdown via specific siRNA application
additional information
generation of a mouse model of smooth muscle cellspecific p110delta deficiency. Targeted deletion of p110delta doe not affect vascular remodeling in vivo. p110 Subunit knockdown via specific siRNA application
additional information
generation of a mouse model of smooth muscle cellspecific p110delta deficiency. Targeted deletion of p110delta doe not affect vascular remodeling in vivo. p110 Subunit knockdown via specific siRNA application
additional information
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generation of a mouse model of smooth muscle cellspecific p110delta deficiency. Targeted deletion of p110delta doe not affect vascular remodeling in vivo. p110 Subunit knockdown via specific siRNA application
additional information
-
generation of p110gamma knockout mice. p110gamma-deficient effector CD8 T cells exhibit impaired migration in vitro and exhibit reduced migration into the inflamed peritoneum following vaccinia virus challenge in vivo. Furthermore, p110gamma-/- mice exhibit reduced influx in response to virus-induced peritonitis and exhibit increased susceptibility to vaccinia virus infection when compared with wild-type mice, phenotype, overview
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additional information
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p110 subunit knockdown via specific siRNA application
additional information
p110 subunit knockdown via specific siRNA application
additional information
p110 subunit knockdown via specific siRNA application
