| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.72500066 |
| Activation of PI3K by glucose dependent insulinotropic polypeptide and glucose was associated with insulin receptor substrate isoforms insulin receptor substrate 2 and growth factor bound 2 associated binder 1 and PI3K isoforms p85alpha , p110alpha , p110beta , and p110gamma . 0.72500066^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| The major cytosolic substrate of the insulin receptor is a 185 kDa phosphoprotein ( IRS 1 ) that contains multiple putative attachment sites for the p 85 alpha regulatory subunit of phosphatidylinositol 3 ' kinase ( PI3K ) . ^^^ The latter was found to undergo specific association with the p 85 alpha regulatory subunit of PI3K but not with two other proteins that contain src homology domains . ^^^ As p 85 alpha was not detectably phosphorylated on tyrosine residues and did not appear to interact directly with the insulin receptor , we conclude that tyrosine phosphorylation of pp 185 promotes its association with p 85 alpha and the catalytic subunit of PI3K . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Finally , tryptic peptide maps show that p56lck phosphorylates three tyrosine residues in the p 85 alpha subunit of PI3K and two in p 110 of PI3K . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| The in vitro phosphorylation of p 85 alpha or p 110 alpha derived from thrombin stimulated platelets was no different than that of resting platelets , but we confirm that in thrombin receptor stimulated platelets enhanced levels of p 85 alpha and PI3K lipid kinase activity were recovered in antiphosphotyrosine antibody immunoprecipitates . ^^^ These results suggest PI3K alpha can autophosphorylate on serine and threonine , and both p 85 alpha and p 110 alpha are substrates for a constitutively associated protein tyrosine kinase in platelets . . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| We fused the inter Src homology region 2 of the regulatory p85alpha subunit of PI3K ( iSH 2 ) either to a C terminal sequence of GLUT 4 ( G4c , amino acids 406 509 ) or to this region and the N terminal tail of GLUT 4 ( G4n , amino acids 1 19 ) , resulting in the fusion proteins iSH 2 G4c and G4n iSH 2 G4c , respectively . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| The mouse gene encoding the PI3K adapter subunit p85alpha and its splice variants p55alpha and p50alpha was disrupted . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| To determine the role of PI3K in glucose homeostasis , we generated mice with a targeted disruption of the gene encoding the p85alpha regulatory subunit of PI3K ( Pik3r1 ; refs 3 5 ) . ^^^ Insulin stimulated PI3K activity associated with insulin receptor substrates ( IRSs ) was mediated via full length p 85 alpha in wild type mice , but via the p 50 alpha alternative splicing isoform of the same gene in Pik3r1 / mice . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Interestingly , a strong association of p85alpha and p110alpha subunits of PI3K with beta catenin is induced in V12Ras expressing keratinocytes , and in vitro binding assays show a direct interaction between beta catenin and p85alpha . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| By using purified preparations we show that nanomolar concentrations of Gbetagamma significantly stimulated lipid kinase activity of phosphatidylinositol 3 kinase ( PI3K ) beta and PI3Kgamma in the presence as well as in the absence of non catalytic subunits such as p85alpha or p 101 . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| In RAW murine macrophages , p 55 , p85alpha , and p85beta PI3K subunits were present at isolated lipid bodies . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| LY 294002 , which inhibits all classes of PI3Ks , strongly suppressed Kit and FcepsilonRI induced responses in p85alpha / mast cells , revealing the contribution of another PI3K family member ( s ) . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| There was no difference in the mRNA abundances of IRS 1 , GLUT 4 , p 85 alpha phosphatidylinositol 3 kinase ( p 85 alpha PI3K ) or Rad . ^^^ In control subjects , the diet increased p 85 alpha PI3K ( +146 % ) , insulin receptor ( +100 % ) and Rad ( +40 % ) mRNA concentrations in muscle . ^^^ In Type 2 diabetic patients , the diet increased insulin receptor ( +41 % ) and Rad ( +31 % ) mRNAs but the expression of p 85 alpha PI3K was not modified . ^^^ CONCLUSION / INTERPRETATION : The regulation of the expression of p 85 alpha PI3K is altered during caloric restriction in skeletal muscle of Type 2 diabetic patients . ^^^ Because we have shown in an earlier study that there is also a defective regulation of p 85 alpha PI3K gene expression in response to insulin , these data support the hypothesis that alterations in the regulation of gene expression could be involved in the pathogenesis of Type 2 diabetes . . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Dexamethasone induces overexpression of the PI3K subunit p85alpha , which , in turn , competes with the complete PI3K heterodimer for binding at insulin receptor substrate 1 , inhibiting PI3K activation . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Ras activation was inhibited by a Grb 2 dominant negative form ( P49L ) , by PI3K inhibitors , including wortmannin , LY 294002 , the N SH 2 domain of p85alpha PI3K and by the SH 2 domain of Src . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Both transformation of Rat 1 fibroblasts by 5 Src or K Ras and stable transfection for expression of dominant positive , wild type phosphoinositide 3 kinase ( PI3K ) regulatory subunit p 85 alpha constitutively led to stress fiber disruption , cortical actin recruitment , extensive ruffling , and macropinosome formation , as measured by a selective acceleration of fluid phase endocytosis . ^^^ These alterations closely correlated with activation of PI3K and phosphatidylinositol specific phospholipase C ( PI PLC ) , as assayed by 3 phosphoinositide synthesis in situ and in vitro and inositol 1 , 4 , 5 trisphosphate steady state levels , respectively ; they were abolished by stable transfection of 5 Src transformed cells for dominant negative truncated p 85 alpha expression and by pharmacological inhibitors of PI3K and PI PLC , indicating a requirement for both enzymes . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Induction of the Cdc 42 pathway is independent of phosphoinositide 3 kinase ( PI3K ) enzymatic activity , but it is dependent on the p85alpha regulatory subunit of PI3K . ^^^ These observations show the essential role of the PI3K regulatory subunit p85alpha in controlling PDGF receptor induced cytoskeletal changes and cell migration , illustrating a novel signaling pathway that links receptor stimulation at the cell membrane with actin dynamics . . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| In humans , the Met326Ile missense variant of the p85alpha regulatory subunit of the phosphoinositide 3 kinase ( PI3K ) has been associated with either significant reductions in glucose effectiveness and intravenous glucose tolerance in Caucasians or a significantly higher insulin secretory response in Pima Indians . ^^^ In the present study , we genotyped 1 , 190 Caucasian males to evaluate the impact in vivo of the Met326Ile variant of the p85alpha subunit of PI3K on the acute insulin response , intravenous glucose tolerance , insulin mediated glucose uptake , and the prevalence of type 2 diabetes after 20 years of follow up . ^^^ We conclude that the Met326Ile variant of the p85alpha regulatory subunit of PI3K is likely to be as functionally normal in vivo as in vitro . . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Activated PI3K is composed of a catalytic subunit ( p110alpha or beta ) associated with one of a large family of regulatory subunits ( p85alpha , p85beta , p55gamma , p55alpha , and p50alpha ) . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| In contrast with previous reports , immunoblots and indirect immunofluorescence failed to detect the p85alpha subunit of the heterodimeric PI3K within VSMC nuclei . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Basal mRNA levels ( determined by reverse transcriptase competitive polymerase chain reaction ) of insulin receptor , insulin receptor substrate 1 , p85alpha phosphatidylinositol 3 kinase ( PI3K ) , p110alphaPI3K , p110betaPI3K , GLUT 4 , glycogen synthase , and sterol regulatory element binding protein 1c ( SREBP 1c ) were similar in muscle of control ( n = 17 ) , type 2 diabetic ( n = 9 ) , type 1 diabetic ( n = 9 ) , and nondiabetic obese ( n = 9 ) subjects . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Moreover , we found that ERalpha binds to the p85alpha regulatory subunit of PI3K in the absence or presence of estradiol in epithelial cells and subsequently activates PI3K / AKT2 , suggesting ERalpha regulation of PI3K / AKT2 through a nontranscriptional and ligand independent mechanism . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Using three independent assays , we demonstrated that the C terminal ( CT ) SH 2 domain , but not the N terminal SH 2 domain , on the PI3K p85alpha subunit displayed discriminative affinity for PIP ( 3 ) . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| We have used single strand conformational polymorphism / heteroduplex analysis to demonstrate the presence of somatic mutations in the gene for the p85alpha regulatory subunit of PI3k ( PIK3R1 ) in primary human colon and ovarian tumors and cancer cell lines . ^^^ Expression of a mutant protein with a 23 amino acid deletion leads to constitutive activation of PI3k providing the first direct evidence that p85alpha is a new oncogene involved in human tumorigenesis . . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| These results suggest either that p85alpha negatively regulates insulin signaling , or that p85beta , which mediates the major fraction of Class IA PI3K signaling in the absence of p85alpha , is more efficient than p85alpha in mediating insulin responses . ^^^ These results indicate that in addition to their roles in recruiting the catalytic subunit of PI3K to the insulin receptor substrate proteins , both p85alpha and p85beta play negative roles in insulin signaling . . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| New responsibilities for the PI3K regulatory subunit p 85 alpha . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Total levels of p85alpha subunit of PI3K and Akt were not influenced by plasma NEFA levels either in the basal state or during the glucose clamps . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Mice that lack the p85alpha regulatory subunit of phosphatidylinositol 3 kinase ( PI3K ) are deficient in gastrointestinal and peritoneal mast cells but have dermal mast cells . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Coimmunoprecipitation studies demonstrated that , in a ligand dependent manner , raloxifene increased ERalpha associated p85alpha , p110alpha , and PI3K activity . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| These include a decreased IRS 2 pool level , a decrease in PI3K activity and its association with IRS 2 and decreased docking of p85alpha to IRS 2 . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| The decreased activity of the insulin / IGF 1 signaling pathway is indicated by decrease of ( a ) IRS two pool levels ; ( b ) docking of p 85 alpha to IRS 2 ; ( c ) docking of p 85 alpha to p 110 alpha or p 110 beta , and ( d ) IRS 2 associated PI3K activity . ^^^ Our data show that the PI3K activity associated with IRS 1 , the docking of IRS 1 to InR beta and the docking of p 85 alpha to IRS 1 are attenuated in the aged Snell dwarf . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Treatment of BT 474 cells with Herceptin inhibited the constitutive tyrosine phosphorylation of HER 3 and disrupted the basal association of HER 3 with HER 2 and of HER 3 with p85alpha potentially explaining the inhibition of PI3K . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| We have utilized p110delta directed Western blotting , RT PCR , PI3K activity assays , and immunoprecipitations of PI3K Class IA subunits p85alpha , p85beta , and p110delta from lysed human platelets , as well as Triton 10 100 insoluble cytoskeletal preparations from resting and thrombin receptor activated platelets . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| AT 2 receptor stimulation did not change insulin induced tyrosine phosphorylation of IRS 2 or its association with the p85alpha subunit of PI3K , but led to a significant reduction of insulin induced p85alpha phosphorylation . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Co immunoprecipitation analysis showed a constitutive association between c Src and PI3K , which was enhanced by PTH treatment , suggesting that the cytosolic tyrosine kinase forms an immunocomplex with PI3K probably via the N SH 2 domain of the p85alpha regulatory subunit . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Phosphoinositide 3 kinases ( PI3Ks ) constitute a family of lipid kinases that regulate an array of fundamental cellular responses by neutrophils [ polymorphonuclear leukocytes ( PMN ) ] . p85alpha Gene disrupted mice were used to help accurately identify the physiological role of the PI3K isoform in PMN activation in the presence of granulocyte macrophage colony stimulating factor ( GM CSF ) . ^^^ In terms of targeting strategy , however , the mutation actually expressed a small amount of Ia type ( p85alpha regulated ) PI3K activity ( partially abrogated ) in the mice . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| The p85alpha regulatory subunit of class 1 ( A ) phosphoinositide 3 kinases ( PI3K ) is derived from the Pik3r1 gene , which also yields alternatively spliced variants p50alpha and p55alpha . ^^^ Although , IGF 1 stimulated PI3K activity associated with insulin receptor substrates was unaltered in all cell lines , p85alpha null ES cells showed diminished protein kinase B activation despite increased PI3K activity associated with the p85beta subunit . ^^^ However , differentiated ES cells partially lost their ability for compensatory signaling at the level of PI3K , which may explain some of the defects observed in mice with homozygous deletion of the Pik3r1 gene . . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| In the present paper , we compare and contrast the phenotypes of p 110 delta mutant mice with those of mice that lack p 85 alpha or p 110 gamma , and discuss these in the context of PI3K signalling in B and T cells . . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Hormone induced tyrosine phosphorylation of p85alpha , the regulatory subunit of PI3K , as well as the phosphorylation on Thr ( 308 ) of its downstream effector Akt / PKB was evident in enterocytes from 3 month old rats , whereas it was greatly reduced in the cells from 24 month old animals . ^^^ Intracellular Ca ( 2+ ) chelation ( BAPTA AM , 5 microM ) affected the tyrosine phosphorylation of p85alpha and inhibited PTH dependent PI3K activation by 75 % in young rats and completely abolished the enzyme activity in aged animals , demonstrating that Ca ( 2+ ) is required for full activation of PI3K in enterocytes stimulated with PTH . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| To investigate the roles that enzymes play in platelet function in vivo and determine which isoforms are important for particular signaling events , we analyzed platelet function of gene knockout mice deficient in the p85alpha regulatory subunit of heterodimeric class IA PI3K . ^^^ Significant attenuation of CRP induced tyrosine phosphorylation in known PI3K effectors such as Btk , Tec , PKB / Akt , and phospholipase Cgamma 2 were observed with p85alpha / platelets , whereas no alteration was noted in upstream molecules of Syk , LAT , and SLP 76 . ^^^ Considered as a whole , these results provide the first genetic evidence that PI3K p85alpha plays a significant role in platelet function , almost exclusively in the glycoprotein ( GP ) VI / Fc receptor gamma chain complex mediated signaling pathway . . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| TSH and cAMP increased the tyrosine phosphorylation of TSHR and the association between TSHR and the p85alpha regulatory subunit of PI3K . ^^^ The TSH induced S6K1 phosphorylation was inhibited by a dominant negative p85alpha regulatory subunit or by the PI3K inhibitors wortmannin and LY 294002 . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| In contrast , overexpression of a dominant negative mutant of the p85alpha regulatory subunit of PI3K ( Deltap 85 ) induced apoptosis . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| The alternative PI3K ( phosphoinositide 3 kinase ) inhibitor LY 294002 ( 100 microM ) and a dominant negative form of the enzyme ( p85alpha DeltaiSH 2 ) induce a more modest vesicle enlargement . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Here we demonstrate that PI3K activation by Reelin requires Src family kinase activity and depends on the Reelin triggered interaction of Dab 1 with the PI3K regulatory subunit p85alpha . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| AR interacts with the p85alpha regulatory subunit of PI3K , and its binding affinity is increased after androgen stimulation . ^^^ Neither N terminal truncated nor proline rich region deleted AR mutants , which are unable to bind to p85alpha and Src , respectively , was able to mediate androgen induced PI3K / Akt activation . ^^^ These findings indicate that a triple complex between AR , p85alpha , and Src is required for androgen stimulated PI3K / Akt activation , and that the PI3K / Akt pathway , in addition to mitogen activated protein kinase , mediates androgen induced cell growth and cell survival . . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Contrary to expectations , four different experiments indicated that PI3K is not necessary for JSRV induced transformation : ( 1 ) cotransfection with a dominant negative truncated form of the PI3K regulatory subunit ( Deltap 85 ) did not affect transformation frequency , ( 2 ) cells stably expressing Deltap 85 showed the same frequencies of transformation as parental NIH 3T3 cells , ( 3 ) fibroblasts established from double knockout mice lacking PI3K p85alpha and p85beta could be transformed with JSRV envelope , and ( 4 ) incubation of cells with the PI3K inhibitor LY 294002 did not specifically inhibit transformation , nor did the drug reverse transformation of JSRV transformed cells . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| We examined the role of class IA PI3K in antigen induced airway inflammation and hyperresponsiveness by i . p . administration into mice of Deltap 85 protein , a dominant negative form of the class IA PI3K regulatory subunit , p85alpha , which was fused to HIV TAT ( TAT Deltap 85 ) . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Three genes ( recombination activating gene 1 ( RAG 1 ) , heat shock 60 kDa protein 1 ( HSP 60 ) , and transforming growth factor beta 1 ( TGF beta 1 ) ) were found to be up regulated more than two fold in CD , whereas four genes ( phosphoinositide 3 kinase regulatory subunit polypeptide 1 [ p 85 alpha ] ( PI3K ) , frizzled homolog 2 [ Drosophila ] , Bcl 2 / adenovirus E1B 19 kDa interacting protein ( NIP 3 ) , and glia maturation factor beta ( GMF beta ) ) were down regulated to less than 50 % of their normal levels . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Nuclear PLZF binds to a consensus sequence of the phosphatidylinositol 3 kinase p 85 alpha subunit ( p 85 alpha PI3K ) gene . ^^^ AT ( 2 ) enhances expression of p 85 alpha PI3K followed by enhanced p 70 ( S 6 ) kinase , essential to protein synthesis . ^^^ This cardiac selective pathway involving AT ( 2 ) , PLZF and p 85 alpha PI3K may explain the absence of a cardiac hypertrophic response in AT ( 2 ) gene deleted mice . . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Notably , p110alpha was silenced without affecting levels of either the other class 1 ( A ) PI3K catalytic subunits p110beta and p110delta , or the p85alpha regulatory subunit . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| PI3K activity was assessed by measuring the phosphorylation of the regulatory subunit p85alpha and kinase activity of the catalytic 110 kDa subunit of PI3K . ^^^ ANG 2 increased the phosphorylation of p85alpha and kinase activity of the 110 kDa PI3K subunit in VSMCs from SHR and transiently increased p85alpha SAM 68 association . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| In addition , analysis of mice lacking individual PI3K genes indicates that products of the Pik3r1 gene contribute to transformation efficiency by BCR ABL . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| We generated an intracellular single chain B 1 8 Fv ( iscFv ) , fused it to the N terminus of the regulatory subunit ( p85alpha ) of phosphatidylinositol 3 kinase ( PI3K ) ( isc p85alpha ) , and examined the potential of this iscFv to serve as an intracellular elutable protein purification tag . ^^^ Furthermore , co purification of the catalytic subunit of PI3K ( p 110 ) was achieved from lysates of co transfected S 2 cells as well as RBL 2H3 mast cells stably expressing isc p85alpha . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| The aim of our study was to investigate whether common polymorphisms in the genes regulating the early insulin signalling pathway ( insulin ; A 23T , insulin like growth factor 1 receptor [ IGF 1R ] ; GAG1013GAA , plasma cell membrane glycoprotein 1 [ PC 1 ] ; K121Q , insulin receptor substrate [ IRS 1 ] ; G972R , insulin receptor substrate 2 [ IRS 2 ] ; G1057D and phosphatidylinositol 3 kinase p 85 alpha [ PI3K ] ; M326I ) affect the weight change and development of Type 2 diabetes in the Finnish Diabetes Prevention Study . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| To further study their unique biochemical properties , the three human Class Ia PI3K ( alpha , beta , and delta ) p 110 catalytic domains were cloned and co expressed with the p85alpha regulatory domain in Sf 9 cells . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| We find that , although the two stimuli result in comparable recruitment of the p85alpha subunit of PI3K into complexes with tyrosine phosphorylated proteins , the p85beta regulatory subunit and p110alpha catalytic subunit of PI3K are preferentially recruited into these complexes in response to IGF 1 . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Expression of p85alpha and Akt mutants , or pretreatment of cells with LY 294002 , a PI3K inhibitor , attenuated sPLA ( 2 ) induced MMP 2 activation and migration . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Tumors exhibited increased association of Egfr with clathrin heavy chain ( CHC ) , Gab 1 , and p85alpha , the regulatory subunit of phosphoinositide 3 kinase ( PI3K ) , and tumors also overexpressed c Src , PDK 1 , and Akt . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| The p85alpha and p110delta subunits of PI3K both participate in anti IgM and mIg / CD19 coligation induced Ca ( 2+ ) flux , although the defects are not as severe as observed after pharmacological inhibition . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Ex vivo biochemical studies of mediobasal hypothalamic tissue revealed that insulin stimulated the association of insulin receptor substrate 1 with the p85alpha subunit of PI3K and also tyrosine phosphorylation of p 42 and p 44 subunits of MAPK in the hypothalamus . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| In clone no . 6 30 in which the gene coding for the p85alpha subunit of phosphoinositide 3 kinase ( PI3K ) was trapped , the expression of marker genes of early chondrocytes including collagen type 2 , aggrecan , and PTH / PTHrP receptor was delayed . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Gene targeting experiments had shown that B cells deficient in p85alpha , an adaptor protein required for PI3K function , were defective in their ability to proliferate in response to BCR stimulation . ^^^ Unexpectedly , they show that while the BCR induced phosphorylation of the PI3K dependent kinase Akt is reduced in p85alpha deficient cells , the phosphorylation of two downstream targets of Akt FOXO 1 and ribosomal protein S 6 is largely unaffected . ^^^ Furthermore , they show that treatment of wild type B cells with PI3K inhibitors had a more profound effect than disruption of the p85alpha gene . ^^^ Taken together , these results indicate that in the absence of p85alpha , there is still significant residual PI3K activity . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| B cell receptor ( BCR ) driven proliferation is completely blocked either in cells lacking the p85alpha regulatory isoform of PI3K or in wild type cells treated with pharmacological PI3K inhibitors . ^^^ Here we show that B cells lacking p85alpha have signaling impairments that are both quantitatively and qualitatively different from those in cells treated with PI3K inhibitors . ^^^ These partial impairments suggest that there are other routes to PI3K activation in B cells apart from p85alpha associated catalytic subunits . ^^^ Notably , addition of phorbol ester restores BCR mediated proliferation in p85alpha deficient cells but not wild type cells treated with PI3K inhibitors . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Furthermore , the association between thyroid hormone receptor beta 1 ( TRbeta 1 ) and PI3K regulatory subunit p85alpha , and the inhibition of T 3 induced PI3K activation and mTOR phosphorylation by a dominant negative TR ( G345R ) demonstrated the involvement of TR in this T 3 action . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| RESULTS : We demonstrated that CM ( Coll ) Listeria / TSB increases the tyrosine phosphorylation level of ErbB 2 and ErbB 3 , members of the epidermal growth factor receptor ( EGFR ) family , and the association between ErbB 3 and the phosphatidylinositol 3 kinase ( PI3K ) regulatory subunit ( p85alpha ) . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Mice lacking p85alpha , the predominant PI3K regulatory isoform , exhibit defects in B cell development and activation that are grossly similar to those found in mice lacking Bruton ' s tyrosine kinase ( Btk ) and other critical signaling molecules . ^^^ These findings establish a role for PI3K p85alpha in differentiation of both follicular and marginal zone B cells , and suggest that these functions are required not solely for the propagation of anti apoptotic signals . . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Moreover , Dex induced an association of GR with the regulatory subunit of PI3K , p85alpha , in a ligand dependent manner and promoted serine / threonine kinase Akt phosphorylation that was blocked by coadministration of mifepristone or LY 294002 . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| In situ hybridization histochemistry revealed that the expression of PI3K regulatory subunit alpha isoforms ( p85alpha , p55alpha , and p50alpha ) was significantly enhanced in injured motor neurons , whereas other regulatory subunits such as p85beta or p55gamma were not detected . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| One glioblastoma exhibited a 9 bp deletion that encompassed the exon intron junction of exon 12 of PIK3R1 , documenting for the first time a mutation within a PI3K regulatory subunit in human glioblastoma . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Unexpectedly , mice lacking either of the PI3K regulatory subunits p85alpha or p85beta exhibit increased insulin sensitivity . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| This identified an increase and reduction in the expression of p110gamma and p85alpha class Ia phosphoinositide 3 kinase ( PI3K ) subunits in recurrent tumor epithelia . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Soriano , Development 124 : 2691 2700 , 1997 ) , suggesting that PI3K is an essential mediator of PDGFRalpha signaling at this developmental stage . p85alpha / p55alpha+ / + p50alpha+ / + p85beta / mice had similar but less severe defects , indicating that p85alpha and p85beta have a critical and redundant function in development . ^^^ |
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| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Both effects are associated to the formation of beta catenin / p85alpha and inhibition of beta catenin / APC complexes and are independent of GSK 3 and PI3K activities . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| The combination of dominant negative src and fyn blocked calcium induced tyrosine phosphorylation of the regulatory subunit of PI3K , p85alpha , and the activity of the catalytic subunit of PI3K . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| The role of the PI3K pathway in pancreatic regeneration after partial Px was assessed by effects of a pharmacologic PI3K inhibitor wortmannin or small interfering RNA ( siRNA ) to the p85alpha regulatory subunit . ^^^ To confirm further the critical role of the PI3K / Akt pathway in pancreatic acinar cell proliferation , IGF 1 mediated cell proliferation was determined in cultured acinar cells pretreated with wortmannin or p85alpha siRNA . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Here , we examined the effect of deleting various regulatory subunits of PI3K ( p85alpha and p85beta ) on epithelial neoplasia and lymphoid hyperplasia in PTEN+ / mice . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| This effect was partially dependent on the PI3K subunits p85alpha and p110gamma . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| In the present study we show that , like B lymphocytes lacking cyclin D 2 , the p85alpha subunit of phosphatidylinositol 3 kinase ( PI3K ) or other components of the B cell signalosome , p110delta null B cells fail to induce cyclin D 2 and enter early G 1 but not S phase of the cell cycle . ^^^ Furthermore , using both p85alpha null and p110delta null B cells and inhibitors of PI3K , this study demonstrates for the first time , that BCR cross linking induces cyclin D 2 mRNA expression via transcriptional activation of the cyclin D 2 promoter and that this transcriptional activation of cyclin D 2 requires PI3K activity . ^^^ Further characterisation of signalling intermediates downstream of the BCR revealed a perturbation of MAPK signalling pathways in p85alpha null and p110delta null B cells , and our data suggests that cross talk exists between the PI3K and JNK pathways . . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| METHODS : Human colon cancer cells KM 20 and KM12C ( both TRAIL resistant ) were transfected with siRNA directed against the PI3K p85alpha regulatory subunit Akt 1 or nontargeting control sequence and then treated with TRAIL ( 100 ng / mL ) or vehicle . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Biochemical expression of the p 110 catalytic and p 85 regulator subunits of PI3K in western analyses revealed no difference in expression of the regulatory p85alpha or p110alpha protein subunits between WKY rats and SHR ; p110gamma was not detected . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| To further understand the role of class 1 ( A ) PI3K in controlling heart growth and to circumvent potential complications from the overexpression of dominant negative and constitutively active proteins , we generated mice with muscle specific deletion of the p85alpha regulatory subunit and germ line deletion of the p85beta regulatory subunit of class 1 ( A ) PI3K . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| We report that , in mouse embryocarcinoma cells ( F 9 cells ) , RA induces an early activation of PI3K and Akt via an increase in the expression of the p85alpha regulatory subunit . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Here we show that in thyroid tumors , PV mutant bound significantly more to the PI3K regulatory subunit p85alpha , resulting in a greater increase in the kinase activity than did TRbeta 1 in wild type mice . ^^^ These results suggest that PV , via the activation of p85alpha , could act to affect PI3K downstream signaling in both the nuclear and extranuclear compartments , thereby contributing to thyroid carcinogenesis . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| We have found that the p 85 alpha subunit of PI3K binds directly to Rab 5 and possesses GTPase activating protein ( GAP ) activity toward Rab 5 . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| In the present study , we demonstrate that the inhibition of PI3K in VSMCs by expression of a dominant negative p85alpha mutant lacking the p 110 binding domain ( Deltap 85 ) , or by treatment of cells with LY 294002 , inhibited Ang 2 stimulated PAI 1 ( plasminogen activator inhibitor 1 ) mRNA expression . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| In the present study , we demonstrate that macrophages deficient for PI3K ( p85alpha regulatory subunit ) are impaired in nitric oxide ( NO ) production upon lipopolysaccharide and interferon gamma stimulation and thus vulnerable for intracellular bacterial infection such as Chlamydophila pneumoniae . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Co immunoprecipitation studies showed a direct interaction of cytosol localized thyroid hormone receptor TRalpha 1 and the p85alpha subunit of PI3K . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| We inhibited PI3K activities by the transient expression following nucleofection of dominant negative mutants of either p85alpha or p110gamma in the human myeloid cell line PLB 985 , which can be induced to express a neutrophil like phenotype . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| The authors determined the pattern of distribution of PI3K pathway components ( ie , the p85alpha regulatory subunit , p110alpha catalytic subunit , Akt 1 , Akt 2 , and the tumor suppressor PTEN ) in human colorectal cancer . ^^^ METHODS : Immunohistochemical analysis was performed on colorectal adenocarcinomas and adjacent normal mucosa for PI3K pathway components , including p85alpha , p110alpha , Akt 1 , Akt 2 , and the tumor suppressor PTEN , which inhibits PI3K . ^^^ RESULTS : PI3K pathway components p85alpha and Akt 2 were highly expressed in glandular elements of colon cancers , with a correlation between staining intensity and clinical stage ; PTEN expression was decreased in the colon cancers of all stages . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Here , we show that mice with a liver specific deletion of the p85alpha regulatory subunit of PI3K ( L Pik3r1KO ) exhibit a paradoxical improvement of hepatic and peripheral insulin sensitivity . ^^^ Thus , the regulatory subunit p85alpha is a critical modulator of insulin sensitivity in vivo not only because of its effects on PI3K activation , but also as a regulator of PTEN activity . . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| The lipid kinase complex , which is made up of p 85 alpha and p 110 alpha regulatory and catalytic subunits , becomes associated with a number of activated receptor protein tyrosine kinases , but the mechanism of its activation has not yet been defined . ^^^ RESULTS : Expression of p 110 alpha , the catalytic subunit of phosphatidylinositol 3 kinase , in the fission yeast , Schizosaccharomyces pombe , has been used to demonstrate an inhibitory effect of p 85 alpha on p 110 alpha activity in intact cells ; inhibition did not result from a decrease in p 110 alpha expression . ^^^ In this cellular context , we have investigated the effect of a constitutively active mutant of Ras , 5 Ras , either on p 85 alpha or p 110 alpha alone , or on the p 85 alpha / p110 alpha complex . ^^^ CONCLUSIONS : The phosphatidylinositol 3 kinase complex , p 85 alpha / p110 alpha , shows a suppressed catalytic function in vivo when compared with free p 110 alpha . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| The regulatory ( p 85 alpha ) and catalytic ( p 110 alpha ) subunits of the mammalian phosphatidylinositol 3 kinase have been expressed in insect cells using the baculovirus sytem . ^^^ The free catalytic subunit p 110 alpha and the coexpressed heterodimeric complex of p 85 alpha and p 110 alpha were purified and their enzymological properties compared . ^^^ Therefore , a post translational modification dependent upon the presence of the regulatory subunit p 85 alpha rather than the physical subunit interaction itself is responsible for the observed properties of the lipid kinase activity of the p 110 alpha . p85 alpha complex . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| To address this question we increased PI3K activity in differentiated 3T3 L 1 adipocytes by adenovirus mediated expression of both the inter SH 2 region of the regulatory p 85 subunit of PI3K ( iSH 2 ) and the catalytic p 110 alpha subunit ( p 110 ) . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| In contrast , the catalytically impaired p 110 alpha mutants as well as the p 85 alpha subunit of P13K were inactive in the fos assay . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| We found that caffeine inhibits the in vitro lipid kinase of class 1 PI3Ks ( IC ( 50 ) = 75 microm for p 110 delta , 400 microm for p 110 alpha and p 110 beta , and 1 mm for p 110 gamma ) , and theophylline has similar effects ( IC ( 50 ) = 75 microm for p 110 delta , 300 microm for p 110 alpha , and 800 microm for p 110 beta and p 110 gamma ) and also inhibits the alpha isoform of class 2 PI3K ( PI3K C 2 alpha ) ( IC ( 50 ) approximately 400 microm ) . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| We find that p 110 alpha phosphorylates p 85 alpha Ser 608 in vivo with significant stoichiometry . ^^^ The functional effects of this phosphorylation are highlighted by mutation of Ser 608 , which results in reduced lipid kinase activity and reduced association of the p 110 alpha catalytic subunit with p 85 alpha . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| The two cell embryo expressed 1 O phosphatidylinositol 3 kinase catalytic subunits p 110 alpha , beta , gamma and delta , and regulatory subunits p 85 alpha and beta . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| OBJECTIVE : Because activating mutations and genomic amplification of the PIK3CA gene , which encodes the p110a catalytic subunit of PI3K , are common in many cancers , we sought to investigate this phenomenon in thyroid tumors . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| We also characterized insulin signaling pathways believed to promote myocyte growth and interact with proliferative responses mediated by G protein coupled receptors , and we assessed myocardial insulin receptor substrate 1 ( IRS 1 ) and p 110 alpha catalytic and p 85 regulatory subunits of phospatidylinositol 3 kinase ( PI3K ) , Akt , MEK , ERK1 / 2 , and S 6 kinase 1 ( S6K1 ) . ^^^ Insulin decreased AT1a R mRNA expression but increased protein levels and increased AT 2 R mRNA and protein levels and phosphorylation of IRS 1 ( Ser374 / Tyr989 ) , MEK1 / 2 ( Ser218 / Ser222 ) , ERK1 / 2 ( Thr202 / Tyr204 ) , S6K1 ( Thr421 / Ser424 / Thr389 ) , Akt ( Thr308 / Thr308 ) , and PI3K p 110 alpha but not of p 85 ( Tyr 508 ) . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| The p 110 catalytic subunit of the PI 3 K associated with tyrosine kinases only when complexed with the p 85 alpha regulatory subunit . ^^^ In contrast , only the p 85 alpha subunit was detectably phosphorylated when PI 3 K was associated with mT : cSrc . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Association of pp36 / 38 with PI 3 K p 85 was confirmed by transfection of a hemagglutinin tagged p 85 alpha cDNA into Jurkat cells followed by anti hemagglutinin immunoprecipitation . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| The objectives of the present study were to examine for genetic variability in the human regulatory p85alpha subunit of PI 3 K , to look for an association between gene variants and NIDDM in a case control study , and to relate identified variability to potential changes in whole body insulin sensitivity and glucose turnover in a phenotype study . ^^^ In conclusion , a codon 326Met > Ile variant in the gene encoding the PI 3 K p85alpha regulatory subunit is found in 31 % of a random sample of young healthy Caucasians . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| For example , microinjection of antibodies , peptides , or recombinant proteins which block the interaction of the SH 2 domains of the PI 3 k p85alpha subunit with tyrosine phosphorylated intracellular targets blocks insulin mediated DNA synthesis . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Consequently , we investigated the interaction between the PI 3 K and profilin employing the GSTp 85 alpha fusion protein and the results indicate a specific interaction between profilin and p 85 alpha . ^^^ The affinity of p 85 alpha / profilin complex to actin increases in the presence of p 85 alpha subunit of PI 3 K as compared to profilin itself . . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Inhibition of PI 3 K activity by nanomolar concentrations of wortmannin and of its expression by transfection with an antisense fragment of p85alpha prevented the differentiative process . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| We now report the crystal structure to 1 . 8 A resolution of the C terminal SH 2 domain ( C SH 2 ) of the P85alpha regulatory subunit of phosphoinositide 3 kinase ( PI 3 K ) . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| BCR targets cyclin D 2 via Btk and the p85alpha subunit of PI 3 K to induce cell cycle progression in primary mouse B cells . ^^^ The p85alpha subunit of PI 3 K and Btk are two crucial components of the B cell receptor ( BCR ) signalling pathway . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| However , CIN 85 did not bind directly to the cytoplasmic domain of TNFR 1 ( TNFR 1 CYT ) but to Src family kinases , Cbl and the p85alpha subunit of phosphatidylinositol 3 kinase ( PI 3 K p85alpha ) . ^^^ Src bound directly to TNFR 1 CYT , but Cbl and PI 3 K p85alpha did not . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Wortmannin and LY 29400 , two PI 3 K inhibitors , suppressed the potentiating effects of MMP 2 and preincubation with MMP 2 enhanced the thrombin induced association of the p85alpha PI 3 K subunit with the cytoskeleton and increased the phosphorylation of PKB . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Moreover , Ang 2 stimulated tyrosine phosphorylation of EGF receptor and p85alpha subunit of PI 3 K accompanied by an increase in their association , which was inhibited by valsartan , and enhanced by PD 123319 . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| In this study , PIK3CA , encoding the p110alpha catalytic subunit of PI3K , is identified as an oncogene involved in upper aerodigestive tract ( UADT ) carcinomas . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| PIK3CA , the alpha catalytic subunit of phosphatidylinositol 3 kinase ( PI3K ) , is in this region . ^^^ Activity of the downstream PI3K effector protein kinase B ( PKB ) was higher in SqCas than in AdCas and was correlated with PIK3CA copy number ( r = 0 . 75 ) , suggesting that these copy number increases contribute to activation of PI3K signaling in SqCas of the lung . . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| PIK3CA , encoding the catalytic subunit p110alpha of phosphatidylinositol 3 kinase ( PI3K ) , is activated in malignant diseases . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| The CDKN2A / B genes encode various components of the Rb and p 53 pathways , and the PIK3CA gene makes a catalytic subunit of the protein phosphatidylinositol 3 OH kinase ( PI3K ) , which is known to be involved in the PI3K / ATK signaling pathways . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Investigation of three genes encoding catalytic subunits of Pi3k ( PIK3CA , PIK3CD , and PIK3C2B ) revealed amplification of PIK3C2B ( 1q32 ) in 6 tumors ( 6 % ) . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| It has recently been reported that somatic mutations within the PI3K subunit p110alpha ( PIK3CA ) are present in human colorectal and other cancers . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| To determine whether PI3Ks are genetically altered in human cancers , we recently analyzed the sequences of the PI3K gene family and discovered that one member , the PIK3CA gene encoding the p110alpha catalytic subunit , was frequently mutated in cancers of the colon , breast , brain and lung . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Recently , mutations in PIK3CA , which encodes the p110alpha catalytic subunit of PI3K , have been identified in various human cancers , including 3 of 12 gastric cancers . ^^^ CONCLUSION : Our data suggested that activation of the PI3K signalling pathway in gastric cancer may be achieved through up regulation or mutation of PIK3CA , in which the latter may be a consequence of mismatch repair deficiency . . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Activation of PI3K / Akt pathway by PTEN reduction and PIK3CA mRNA amplification contributes to cisplatin resistance in an ovarian cancer cell line . ^^^ A low level of PTEN expression was strongly associated with amplified PIK3CA and PI3K / Akt activities in OVCAR 3 / CDDP cells . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Mutations in the PIK3CA gene , which encodes the p110alpha catalytic subunit of phosphatidylinositol 3 kinase ( PI3K ) , have been reported in human cancers , including colorectal cancer . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Treatment with the PI3K inhibitor LY 294002 abrogated PIK3CA signaling and preferentially inhibited growth of PIK3CA mutant cells . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| These links were further strengthened by studies showing that the tumour suppressor , PTEN , is an antagonist of PI3K signalling and that somatic mutations of p110alpha ( PIK3CA ) are present in a variety of cancers . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| A wide variety of tumours show PIK3CA mutations leading to increased phosphatidylinositol 3 kinase ( PI3K ) activity . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Here , we investigated two further Pi3k / Akt pathway genes , namely PIK3CA ( 3q26 . 3 ) and phosphatidylinositol 3 kinase enhancer ( PIKE ) ( CENTG 1 , 12q14 ) , for genetic alteration and aberrant expression in a series of 97 primary glioblastomas . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| The PIK3CA gene encodes the p110alpha catalytic subunit of PI3K , and is amplified in some ovarian cancers , whereas the AKT 2 gene is amplified in some ovarian , breast , and pancreatic cancers . ^^^ Recently , in a mutational screen of eight PI3K genes and eight PI3K like genes , PIK3CA was found to be the only gene affected by somatic mutations , which were observed frequently in gastrointestinal and brain cancers . ^^^ CONCLUSIONS : These data indicate that mutations of PIK3CA play an oncogenic role in substantial fractions of ovarian and breast carcinomas , and in consideration of mutation of other components of the PI3K AKT pathway in both tumor types , confirm the major oncogenic role of this pathway in ovarian and breast carcinomas . . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Molecular analysis of the PI3K AKT pathway in uterine cervical neoplasia : frequent PIK3CA amplification and AKT phosphorylation . ^^^ The putative oncogene PIK3CA located in this region encodes a phosphatidylinositol 3 kinase ( PI3K ) . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Recently , it has been reported that somatic mutations within the PI3K catalytic subunit , PIK3CA , are common ( 25 40 % ) among colorectal , gastric , breast , ovarian cancers , and high grade brain tumors . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| In addition to inactivation of the PTEN tumor suppressor gene , mutations or amplifications of the catalytic subunit alpha of PI3K ( PIK3CA ) have been reported . ^^^ Knocking down PTEN expression in the HEC 1B cell line , which possesses both K Ras and PIK3CA mutations , further enhances phosphorylation of Akt ( Ser 473 ) , indicating that double mutation of PIK3CA and PTEN has an additive effect on PI3K activation . ^^^ Our data suggest that the PI3K pathway is extensively activated in endometrial carcinomas , and that combination of PIK3CA / PTEN alterations might play an important role in development of these tumors . . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Recently , mutations in the gene encoding the p110alpha catalytic subunit of PI3K ( PIK3CA ) have been identified in several human cancers . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Deregulation of the phosphatidylinositol 3 kinase ( PI3K ) pathway either through loss of PTEN or mutation of the catalytic subunit alpha of PI3K ( PIK3CA ) occurs frequently in human cancer . ^^^ Furthermore , the association between ERBB 2 overexpression and PIK3CA mutation implies that more than one input activating the PI3K / AKT pathway may be required to overcome intact PTEN . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| A recent study revealed that the p110alpha ( PIK3CA ) , catalytic subunit of phosphatidylinositol 3 kinase ( PI3K ) , is somatically mutated in many types of cancer . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| The recent discoveries of cancer specific mutations in PIK3CA , the gene that encodes the catalytic subunit p110alpha of PI3K , have heightened the interest in the oncogenic potential of this lipid kinase and have made p110alpha an ideal drug target . . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| RECENT FINDINGS : More than 30 % of various solid tumor types were recently found to contain mutations in PIK3CA , the catalytic subunit of PI3K . ^^^ Mutant members of the PI3K pathway , including PIK3CA , are good targets for therapeutic intervention because most of them are kinases , making them attractive for drug development . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| Mutation of PIK3CA , the gene coding for the p110alpha catalytic subunit of phosphoinositide 3 kinase ( PI3K ) , has been reported in a limited range of human tumors . ^^^ No somatic changes were detected in PIK3CB This study extends previous observations in other tumor types by demonstrating the presence of somatic PIK3CA mutations in both SCC and adenocarcinoma of the esophagus , thus implicating the PI3K pathway in the initiation and / or progression of esophageal cancers . . ^^^ |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42336 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|