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evolution
class 1 phosphoinositide 3-kinases are heterodimers consisting of an 85 kDa regulatory/adapter subunit (p85) coupled to a 110 kDa catalytic subunit (p110) with both subunits possessing several isoforms. The class I enzymes are further subdivided into two subclasses: class Ia and class Ib. The class 1a phosphoinositol 3-kinases (p110alpha, p110beta and p110delta) signal downstream of tyrosine kinases, while the single class Ib phosphoinositol 3-kinase (p110gamma) operates downstream of heterotrimeric GPCRs (G-protein-coupled receptors)
evolution
class I PI3K genes control the activity of PI3K/AKT signaling and are often genetically altered in glioblastoma. Class II PI3K genes are implicated in regulating angiogenesis and cilium function. Class III PI3K genes are primarily involved in the regulation of autophagy. Compared to other class IA PI3K isoforms, PIK3CB is the only PI3K catalytic subunit that showed a strong association with recurrence rate, risk, and prognosis
malfunction
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aberrant activation of the phosphatidylinositol 3-kinase pathway is involved in a wide range of cancers. Mutations in subunit isoform p110alpha are involved in development of bladder cancer, and are also common in the benign skin lesions seborrheic keratosis and epidermal nevi
malfunction
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aberrant PI3K signaling has been found to play an important role in multiple aspects of tumorgenesis including uncontrolled proliferation, resistance to apoptosis, angiogenesis and metastatic capability. The PI3Kbeta isoform is implicated as necessary for transformation induced by the loss or inactivation of the PTEN tumor suppressor both in vitro and in vivo
malfunction
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binding of thyroid receptor to p85alpha activates PI3K/AKT signaling promoting thyroid carcinogenesis by increasing cell proliferation and tumor metastasis
malfunction
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chronic blockade of phosphatidylinositol 3-kinase in the nucleus tractus solitarii is prohypertensive in the spontaneously hypertensive rat
malfunction
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constitutively activated phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin, mTOR, signaling is a common feature of T-cell acute lymphoblastic leukemia, where it strongly influences growth and survival
malfunction
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deregulated signaling through phosphatidylinositol 3'-kinase pathway is common in many types of malignancies, including mantle cell lymphoma. PI3K catalytic subunit alpha gene amplification contributes to the pathogenesis of mantle cell lymphoma. Inhibition of PIK3CA induces apoptosis in mantle cell lymphoma cell lines
malfunction
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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
malfunction
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inhibition of PI3-kinase or expression of a dominant negative form of PI3-kinase cause inhibition of airway epithelial cell wound closure
malfunction
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PI3K is involved in non-small cell lung cancer and is PI3K is required for malignant progression in lung cancer, regulation mechanisms, overview
malfunction
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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
malfunction
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PI3Ks constitute important regulators of various signaling pathways with relevance in cancer. Activation of PI3K by membrane localization of subunit p110alpha predisposes mammary glands to neoplastic transformation
malfunction
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PI3Ks constitute important regulators of various signaling pathways with relevance in cancer. Enhanced activation of p110A, the catalytic subunit of PI3K, woccurs in a high proportion of many human tumor types. Activation of PI3K by membrane localization of subunit p110alpha predisposes mammary glands to neoplastic transformation. Perturbation of the interaction of the CDK4/Rb/E2F cascade and the PI3K signaling occurs in many human cancers
malfunction
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suppression of the PI3K catalytic subunit p110alpha inhibits the growth of ovarian cancer cells in vitro and in vivo, inhibiting decreased cell viability and induced cell apoptosis
malfunction
isoproterenol-induced EGFR transactivation is abolished in PI3Kgamma null mutants or through enzyme inhibition by wortmannin or LY-294002
malfunction
p110delta deficiency did not affect vascular remodeling in vivo
malfunction
p110delta deficiency did not affect vascular remodeling in vivo
malfunction
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Plasmodium berghei ANKA-infected PI3Kgamm knockout mice show greater survival despite similar parasitemia levels in comparison with infected wild-type mice. Histopathological analysis demonstrates reduced hemorrhage, leukocyte accumulation and vascular obstruction in the brain of infected PI3Kgamma null mice. PI3Kgamma deficiency also causes lower microglial activation and T cell cytotoxicity in the brain. On day 6 post-infection, CD3+/CD8+ T cells are significantly reduced in the brain of infected PI3Kgamma null mice when compared to infected wild-type mice and expression of CD44 in CD8+ T cell population in the brain tissue and levels of phospho-IkappaB-alpha in the whole brain are also markedly lower in infected PI3Kgamma null mice, phenotype, overview
malfunction
the PI3Kalpha signaling pathway is activated in numerous cancers, where the PI3KCA gene, which encodes for the p110alpha PI3Kalpha subunit, is mutated. Oncogenic mutations that are far from the catalytic site and increase the enzymatic affinity, destabilize the p110alpha/p85alpha dimer. By affecting the dynamics of the protein, these mutations favor the conformations that reduce the autoinhibitory effect of the p85alpha nSH2 domain. Molecular dynamics simulations suggest that all the tumor-associated mutations effectively weaken the interactions between the p110alpha and the p85alpha subunits by disrupting key stabilizing interactions
malfunction
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a combination of INPP4B overexpression and rucaparib blocks the PI3K/AKT signal pathway
malfunction
a patient with a somatic gain of function PIK3CA-mutation (a pathogenic heterozygous missense mutation in PIK3CA) shows extensive multisystem overgrowth, clinical diversity of the PIK3CA-related overgrowth spectrum (PROS), phenotype, overview. The patient has overlapping features of congenital lipomatous overgrowth vascular malformations epidermal nevi and skeletal abnormalities (CLOVES) syndrome and megalencephaly-capillary malformation polymicrogyria (MCAP) syndrome
malfunction
PIK3CA subunit mutations have no correlation with recurrence rate of glioblastoma. Knockdown of PIK3CA/p110alpha in a panel of glioblastoma cell lines shows that loss of PIK3CA/p110alpha fails to both inactivate AKT and block the survival of A172, U87MG, SF295, and U251 glioblastoma cells. Compared to PIK3CA, oncogenic PIK3CB mutations are rare in glioblastoma. Knockdown or inhibitors of PIK3CD/p110delta fails to inhibit AKT and cell viability
malfunction
treatment of cells with the PI3K inhibitor wortmannin, significantly attenuates GLUT4 exocytosis. Cellular deficiency of insulin signaling machineries dampens the expression of the insulin signaling proteins and obliterates downstream signaling mediated through the PI3K pathway
malfunction
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Plasmodium berghei ANKA-infected PI3Kgamm knockout mice show greater survival despite similar parasitemia levels in comparison with infected wild-type mice. Histopathological analysis demonstrates reduced hemorrhage, leukocyte accumulation and vascular obstruction in the brain of infected PI3Kgamma null mice. PI3Kgamma deficiency also causes lower microglial activation and T cell cytotoxicity in the brain. On day 6 post-infection, CD3+/CD8+ T cells are significantly reduced in the brain of infected PI3Kgamma null mice when compared to infected wild-type mice and expression of CD44 in CD8+ T cell population in the brain tissue and levels of phospho-IkappaB-alpha in the whole brain are also markedly lower in infected PI3Kgamma null mice, phenotype, overview
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metabolism
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PI3K is part of the PI3K signaling pathway that is upregulated in cancer
metabolism
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PI3K/Akt/mTOR signaling, overview
metabolism
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Rac1 regulates peptidoglycan-induced nuclear factor-kappaB activation and cyclooxygenase-2 expression in RAW 264.7 macrophages by activating the phosphatidylinositol 3-kinase/Akt pathway
metabolism
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the phosphatidylinositol 3-kinase pathway is a critical signal transduction pathway that regulatesmultiple cellular functions, class IA PI3K signalling pathway, overview
metabolism
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the signaling cascade involving the enzyme is known as the PI3K/Akt/mTor axis
metabolism
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WASP activation downstream of CSF-1R is phosphatidylinositol 3-kinase- and Cdc42-dependent consistent with an involvement of these molecules in macrophage migration, regulation, overview
metabolism
analysis of the mechanism by which phosphatidylinositol 4-phosphate 5-kinase Igammai2 and PI3K are integrated into a complex regulated by Src, resulting in the spatial generation of PIP2, which is the substrate PI3K required for PIP3 generation and subsequent Akt activation, the PIP2-generating enzyme controls Akt activation upstream of a PI3K enzyme
metabolism
the enzyme is involved in isoproterenol-induced EGFR transactivation
metabolism
analysis of the PI3K signaling cascade, overview
metabolism
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inositol polyphosphate-4-phosphatase type II and rucaparib treatment inhibit the growth of osteosarcoma cells dependent on phosphoinositide 3-kinase/protein kinase B pathway, combined effects of INPP4B and rucaparib on cell cycle, apoptosis and phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signal pathway. INPP4B plays an important role in the development of tumors, which can maintain the balance of internal inositol phosphate, suppress the activation of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT) signal pathway, and block cells malignant transformation
metabolism
PIK3CB/p110beta-dictated survival pathway in glioblastoma, overview
physiological function
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activation of phosphatidylinositol 3-kinase is required for tumor necrosis factor-alpha-induced upregulation of matrix metalloproteinase-9
physiological function
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isozyme PI3Kgamma is involved in inteleukin-8-induced increase of endothelial monolayer permeability and is able to limit neovascularization and choroidal edema, as well as macrophage infiltration, therefore contributes to reduce laser-induced retinal damage
physiological function
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isozyme PI3Kgamma is involved in inteleukin-8-induced increase of endothelial monolayer permeability and is able to limit neovascularization and choroidal edema, as well as macrophage infiltration, therefore contributes to reduce laser-induced retinal damage
physiological function
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p110 isoforms alpha, beta, and gamma PI3K are involved in T-cell acute lymphoblastic leukemia cell survival, but not p110delta PI3K
physiological function
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phosphatidylinositol 3-kinase activity and asymmetrical accumulation of F-actin are necessary for establishment of cell polarity in the early development of monospores from the marine red alga. Establishment of the anterior-posterior axis in migrating monospores is PI3K-dependent
physiological function
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phosphatidylinositol 3-kinase is a key mediator of oncogenic K-ras
physiological function
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phosphatidylinositol 3-kinase is involved in sperm-induced tyrosine kinase signaling in Xenopus egg fertilization. Inhibition of sperm-induced activation of the tyrosine kinase Src and a transient increase in the intracellular concentration of Ca2+ at fertilization, overview. PIP3 acts as a positive regulator of the Src signaling pathway in Xenopus fertilization
physiological function
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phosphatidylinositol 3-kinase mediates non-opsonic phagocytosis of Legionella pneumophila by macrophages
physiological function
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PI 3-kinase activated in response to cAMP or IGF-I stimulus plays important roles in increasing the translation rate or mRNA levels of cyclin D1, respectively. Activation of PI 3-kinase in response to cAMP or IGF-I are essential for marked increases in G1 CDK activities and DNA synthesis. cAMP-dependent PI 3-kinase activation plays an important role in the increase in cyclin D1 translation. In contrast, IGF-I-dependent PI 3-kinase activation is required for the increase in cyclin D1 mRNA levels and degradation of p27Kip1
physiological function
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PI 3-kinase is an important enzyme in the early insulin signaling cascade and plays a key role in insulin-mediated glucose transport
physiological function
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PI3-kinase regulates Rac1 activity through the guanosine exchange factor Tiam1. Expression of mutant CA-PI3K causes a significant increase in membrane-associated Tiam1
physiological function
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PI3K activation results in increased cell proliferation, motility, migration, and metastasis. Inhibition of PI3K signaling delays tumor progression and blocks metastasis of thyroid cancer
physiological function
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PI3K, via p85alpha and p85beta subunit isoforms, plays dual regulatory roles in the induction of IFN responses by controlling both IFNalpha- and IFNgamma-dependent transcriptional regulation of IFN-sensitive genes and simultaneously regulating the subsequent initiation of mRNA translation for such genes
physiological function
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selective regulation of CD8 effector T cell migration by the p110gamma catalytic subunit isoform of phosphatidylinositol 3-kinase
physiological function
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the enzyme plays a pivotal role in the mechanism of CSF-1-induced Wiskott-Aldrich syndrome protein activation in vivo
physiological function
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the p110gamma isoform of phosphatidylinositol 3-kinase regulates chemokine receptor-mediated migration of effector CD4 T lymphocytes into peripheral inflammatory sites. Although p110gamma does not regulate antigen-dependent CD4 T cell activation and proliferation, it plays a crucial role in regulating CD4 effector T cell migration, overview
physiological function
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the p85alpha subunit of class IA phosphatidylinositol 3-kinase regulates the expression of multiple genes involved in osteoclast maturation and migration
physiological function
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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
physiological function
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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
physiological function
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Tiam1-mediated Rac1 activation and E-cadherin-mediated cell-cell adhesion are dependent on PI3K activity, regulation, overview. The signaling hierarchy leads from PI3K to Tiam1 to Rac to the actin cytoskeleton resulting in adherens junction formation. PI3K is involved in E-cadherin-dependent regulation of epithelial cell differentiation and polarity
physiological function
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Tiam1-mediated Rac1 activation and E-cadherin-mediated cell-cell adhesion are dependent on PI3K activity, regulation, overview. The signaling hierarchy leads from PI3K to Tiam1 to Rac to the actin cytoskeleton resulting in adherens junction formation. PI3K is involved in E-cadherin-dependent regulation of epithelial cell differentiation and polarity
physiological function
in tumor cell lines and primary patient samples representing multiple B-cell malignancies, constitutive phosphatidylinositol-3-kinase pathway activation is dependent on isoform PI3Kdelta. Inhibitor 3-phenyl-2-[(S)-1-(9H-purin-6-ylamino)-propyl]-3H-quinazolin-4-one blocks constitutive phosphatidylinositol-3-kinase signaling, resulting in decreased phosphorylation of Akt and other downstream effectors, an increase in poly(ADP-ribose) polymerase and caspase cleavage and an induction of apoptosis
physiological function
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isoform PI3Kdelta is responsible for phosphorylation of colony-stimulating factor CSF-1 receptor phosphorylation in response to CSF-1 added to intact cells or isolated nuclei and its triggering of the phosphorylation of Akt and p27 inside the nucleus. Translocation of exogenous CSF-1 to the nucleus-associated CSF-1 receptors correlates with a prominent role of isoform PI3Kdelta in activation of the Rab5 GTPase
physiological function
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phosphatidylinositol 3-kinase is critical for the TLR2 downstream effects of glucocorticoids. Cells expressing a phosphatidylinositol 3-kinase p85 subunit deletion mutant and exposed to Pam3-Cys-Ser-Lys4 in the presence or absence of dexamethasone, show enhanced tumour necrosis factor TNFalpha expression while AP-1 and NF-kappaB transcriptional activity are repressed. Phosphatidylinositol 3-kinase physically interacts with the glucocorticoid receptor through two putative phosphatidylinositol 3-kinase recruitment consensus YxxM binding motifs in the glucocorticoid receptor. The phosphatidylinositol 3-kinase-glucocorticoid receptor interaction may contribute to the effects of glucocorticoids on the TLR2 pro-inflammatory signalling cascade
physiological function
phosphatidylinositol 3-kinase pathway inhibition is sufficient to reduce expression of Smad anchor for receptor activation protein, i.e. SARA. Phosphatidylinositol 3-kinase-dependent depletion of SARA is apparent within 6 h and does not occur at the mRNA or promoter level but is blocked by inhibition of proteasome-mediated degradation. It is a direct effect of phosphatidylinositol 3-kinase subunit alpha action, and coimmunoprecipitation of SARA and subunit alpha confirm that these proteins interact. Expression of GTPase-deficient Rab5 leads to endosomal enlargement and reduced SARA protein expression, similar to that seen with phosphatidylinositol 3-kinase inhibition
physiological function
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suppressing phosphatidylinositol 3-kinase activity by inhibitors LY294002 and PI103 selectively reduces both the mRNA and protein levels of peroxisome proliferator-activated receptor gamma coactivator PGC-1beta but not PGC-1alpha. Reducing PGC-1b expression also leads to reduced mRNA expression levels of uncoupling protein 1, 2 and superoxide dismutase 2. Correspondingly, mitochondrial membrane potential and reactive oxygen species levels are increased
physiological function
class Ia phosphatidylinositol 3-kinase isoform p110alpha is crucial for receptor tyrosine kinases signaling, thus affecting proliferation, migration, and survival of smooth muscle cells, Receptor tyrosine kinasesinduced phosphatidylinositol 3'-kinase signaling via the p110alpha isoform plays a central role for vascular remodeling
physiological function
class Ia phosphatidylinositol 3-kinase isoform p110alpha is crucial for receptor tyrosine kinases signaling, thus affecting proliferation, migration, and survival of smooth muscle cells, Receptor tyrosine kinasesinduced phosphatidylinositol 3'-kinase signaling via the p110alpha isoform plays a central role for vascular remodeling
physiological function
class Ia phosphatidylinositol 3-kinase isoform p110alpha is crucial for receptor tyrosine kinases signaling, thus affecting proliferation, migration, and survival of smooth muscle cells, Receptor tyrosine kinasesinduced phosphatidylinositol 3'-kinase signaling via the p110alpha isoform plays a central role for vascular remodeling
physiological function
class Ia phosphatidylinositol 3-kinase isoform p110beta is disensible for receptor tyrosine kinases signaling, not affecting proliferation, migration, and survival of smooth muscle cells
physiological function
class Ia phosphatidylinositol 3-kinase isoform p110beta is disensible for receptor tyrosine kinases signaling, not affecting proliferation, migration, and survival of smooth muscle cells
physiological function
class Ia phosphatidylinositol 3-kinase isoform p110delta is disensible for receptor tyrosine kinases signaling, p110delta exerts noncatalytic functions in smooth muscle cell proliferation, but had no effect on migration
physiological function
class Ia phosphatidylinositol 3-kinase isoform p110delta is disensible for receptor tyrosine kinases signaling, p110delta exerts noncatalytic functions in smooth muscle cell proliferation, but had no effect on migration
physiological function
class Ia phosphatidylinositol 3-kinase isoform p110delta is disensible for receptor tyrosine kinases signaling, p110delta exerts noncatalytic functions in smooth muscle cell proliferation, but had no effect on migration
physiological function
enzyme PI3K is rapidly recruited to activated growth factor receptors (SH2 domain of the adaptor subunit mediating the interaction to the phosphorylated YXXM motif of the receptor) or integrin-mediated adhesion complex (via interaction with focal adhesion kinase in the adhesion complex), promoting its activation and 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate synthesis. phosphatidylinositol 4-phosphate 5-kinase Igamma, EC 2.7.1.68, is the major PIPKI enzyme contributing to PI3K/Akt signaling in response to activation of growth factor and adhesion receptors in suspension condition, overview
physiological function
non-canonical regulation of phosphatidylinositol 3-kinase gamma isoform activity in retinal rod photoreceptor cells. The interaction between the gamm isozyme and alpha subunit of cyclic nucleotide-gated channel, CNGA1, through its RA domain does not appear to play a role in regulation of CNG channel activity, but phosphatidylinositol 3-kinase gamma uses CNGA1 as an anchoring module to achieve close proximity to its substrate to generate D3-phosphoinositides. CNGA1-associated PI3Kgamma activity is independent of dark and light conditions, as well as insulin receptor impairment in rods. The RA domain of isozyme PI3Kgamma interacts strongly with CTR-CNGA1, compared with the RA domain of isozyme PI3Kalpha in retinal photoreceptor cells
physiological function
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phosphatidylinositol 3-kinase gamma is central in signaling diverse cellular functions. Relevance of isozyme PI3Kgamma for the outcome and the neuroinflammatory process triggered by Plasmodium berghei ANKA infection
physiological function
phosphatidylinositol 4,5-bisphosphate is essential for recognition of the plasma membrane inner leaf by protein complexes. Elimination of phosphatidylinositol 4,5-bisphosphate by its conversion into 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate, a lipid naturally missing in this yeast. The loss of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate leads to loss of actin function and endocytosis defects, causing a blockage in polarized secretion. Also, the cell wall integrity mitogen-activated protein kinase pathway is activated, triggering a typical transcriptional response. In the absence of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate at the plasma membrane, the Pkc1 protein kinase upstream the cell wall integrity mitogen-activated protein kinase pathway module localizes to post-Golgi endosomes marked by SNARE Snc1 and Rab GTPases Ypt31 and Ypt32. Phosphatidylinositol 4,5-bisphosphate depletion activates the CWI pathway and generates a transcriptional profile reminiscent of that induced by cellwall aggressions. PI3K effects in yeast signaling and trafficking are reversible by a competitive inhibitor in a dose-dependent manner
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. The PI3K lipid kinase activity is not essential for regulating cell survival
physiological function
the generation of phosphatidylinositol (3,4,5)-tris-phosphate (PIP3) by the lipid kinase function stabilizes beta2AREGFR complexes while the protein kinase activity of PI3K regulates Src activation by direct phosphorylation. The lipid kinase activity of PI3K is responsible for beta2AREGFR complex formation. Phosphorylation of Src by phosphoinositide 3-kinase regulates beta-adrenergic receptor-mediated EGFR transactivation. EGFR transactivation is a mechanism by which the EGF receptor is stimulated, internalized, and downstream signaling initiated following agonist stimulation by a GPCR, such as the beta-adrenergic receptor. The protein kinase activity of PI3K phosphorylates serine residue 70 on Src to enhance its activity and induce EGFR transactivation following beta-adrenergic receptor stimulation. This additional function for PI3K, whereby Src is a substrate for the protein kinase activity of enzyme PI3K, is of importance since Src plays a key role in pathological and physiological signaling
physiological function
the PI3Kalpha signaling pathway plays an important role in cell growth, proliferation and survival. This pathway is activated in numerous cancers, where the PI3KCA gene, which encodes for the p110alpha PI3Kalpha subunit, is mutated. Physiological activation of PI3Kalpha is triggered by binding of phosphorylated tyrosine kinase receptors RTK or their accessory proteins, such as the insulin receptor substrate 1, IRS-1, that bridge the interaction between RTK and PI3Kalpha
physiological function
phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) plays a critical role in the pathogenesis of cancer including glioblastoma, the most common and aggressive form of brain cancer. Analysis of the role of class IA PI3K catalytic subunits in glioblastoma, overview. siRNAs or shRNAs of PIK3CB, but not shRNAs of PIK3CA, inhibits the growth of U-87MG cells. Subunit PIK3CD/p110beta plays a dispensable role in the disease progression of glioblastoma. Receptor tyrosine kinases (RTKs) or G protein-coupled receptors (GPCRs) selectively activates PIK3CB/p110beta (but not PIK3CA/p110alpha or PIK3CD/p110delta), leading to production of phosphatidylinositol-3,4,5-triphosphate (PIP3) and subsequent phosphorylation of AKT. Divergent roles of class I PI3K genes in normal and malignant tissues, overview
physiological function
phosphatidylinositol-4,5-bisphosphate 3-kinases (PI3Ks) are regulatory enzymes involved in the generation of lipid species that modulate cellular signaling pathways through downstream effectors to influence a variety of cellular functions. Stimulation of PI3K can enhance lysosomal trafficking events to the plasma membrane. Insulin-induced activation of PI3K alters glucose transporter GLUT4 recycling, positive regulatory role for PI3K pathway in the GLUT4 receptor recycling process. PI3K demonstrates both positive and negative regulation of insulin release. The p110gamma subunit of type I PI3K is required to maintain a ready pool of insulin loaded vesicles for the recruitment of insulin granules in the islet beta-cells for release upon exocytic stimulation. PI3K C2alpha, a class II PI3K isoform, exerts signaling effects on insulin secretion from pancreatic beta-cells by promoting insulin loaded granules in insulinoma cells. PI3K is also known to contribute to glucose homeostasis by regulating beta-cell gene expression
physiological function
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phosphatidylinositol 3-kinase activity and asymmetrical accumulation of F-actin are necessary for establishment of cell polarity in the early development of monospores from the marine red alga. Establishment of the anterior-posterior axis in migrating monospores is PI3K-dependent
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physiological function
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selective regulation of CD8 effector T cell migration by the p110gamma catalytic subunit isoform of phosphatidylinositol 3-kinase
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physiological function
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phosphatidylinositol 3-kinase gamma is central in signaling diverse cellular functions. Relevance of isozyme PI3Kgamma for the outcome and the neuroinflammatory process triggered by Plasmodium berghei ANKA infection
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additional information
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SHIP downregulates PI3-K-initiated signals by dephosphorylating PI-3,4,5-triphosphate
additional information
N-terminal tags on the catalytic (p110) subunit of phosphoinositol 3-kinase increase cell signalling and oncogenic transformation, the increase in cell signalling and oncogenic-like transformation in response to p110 NTT is not mediated via an increase in the lipid kinase activity of the enzyme, but may be mediated by increased p110 autophosphorylation and/or other intracellular protein/protein interactions. Tagged recombinant protein is suitable for use in in vitro lipid kinase screens to identify phosphoinositol 3-kinase inhibitors, while in vivo (including intracellular) experiments and investigations into the protein kinase activity should be conducted with untagged constructs
additional information
N-terminal tags on the catalytic (p110) subunit of phosphoinositol 3-kinase increase cell signalling and oncogenic transformation, the increase in cell signalling and oncogenic-like transformation in response to p110 NTT is not mediated via an increase in the lipid kinase activity of the enzyme, but may be mediated by increased p110 autophosphorylation and/or other intracellular protein/protein interactions. Tagged recombinant protein is suitable for use in in vitro lipid kinase screens to identify phosphoinositol 3-kinase inhibitors, while in vivo (including intracellular) experiments and investigations into the protein kinase activity should be conducted with untagged constructs
additional information
the class IA PI3K gene family consists of three highly homologous catalytic subunits PIK3CA, PIK3CB, and PIK3CD (PI3K catalytic subunit alpha, beta, and delta) that encode p110alpha, p110beta, and p110delta, respectively. These subunits form a complex with any of five regulatory subunits p85alpha, p55alpha (a splicing variant of p85alpha), p50alpha (a splicing variant of p85alpha), p85beta, and p55gamma, encoded by PIK3R1, PIK3R2, and PIK3R3 (PI3K regulatory subunit 1, 2, and 3), respectively. Class IB PI3K is composed of one catalytic subunit p110gamma encoded by PIK3CG (PI3K catalytic subunit gamma)and two regulatory subunits: p101 encoded by PIK3R5 (PI3K regulatory subunit 5) and p87 (also known as p84 or p87PIKAP) encoded by PIK3R6 (PI3K regulatory subunit 6). The amino acid K342 in wild-type p110beta exhibits structural changes (i.e. disrupted interactions between p110beta and its regulatory partner p85), which endows p110beta with an unusually high transformation potential similar to the oncogenic p110alpha mutant p110alpha-N345K