Pubmed abstracts for Protein-Protein Interaction search result :


Interacting proteins: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 and P27986 Pubmed SVM Score :0.0
New responsibilities for the PI3K regulatory subunit p 85 alpha . ^^^
Interacting proteins: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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 . ^^^
Interacting proteins: P42338 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: P42338 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: P42338 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: P42338 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: P42338 and P27986 Pubmed SVM Score :0.0
This effect was partially dependent on the PI3K subunits p85alpha and p110gamma . ^^^
Interacting proteins: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 and P27986 Pubmed SVM Score :0.0
We present evidence that expression of phosphatidylinositol 3 kinase ( PI3K ) beta is necessary and sufficient to transmit signals from G proteins to Akt in these murine fibroblasts and that the activation of PI3Kbeta may represent the most likely mechanism whereby GPCRs stimulate Akt , as the vast majority of cells do not express PI3Kgamma , a known G protein sensitive PI3K isoform . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
We have previously shown an important function of phosphatidylinositol 3 kinase ( PI3K ) alpha ( p85alpha p110alpha ) and PI3Kbeta ( p 85 alpha p110beta ) for DNA synthesis induced by various mitogens in non transformed fibroblasts and we now report a specific role of these enzymes in human colon cancer cell growth . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
These results suggest that endogenous PI3Kbeta but not PI3Kalpha is specifically involved in PDGF receptor induced stimulation of Ca ( 2+ ) channels and that different isoforms of PI3K regulate physiological increases of Ca ( 2+ ) influx in vascular myocytes stimulated by vasoconstrictor or growth factor . . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
In addition , we demonstrated that the expressions of p85alpha and p55alpha regulatory subunits of PI 3 kinase were reduced ( p85alpha , 67 % ; p55alpha , 54 % ) , and that the p50alpha regulatory subunit was markedly upregulated ( 176 % ) in the livers of fatty rats without apparent alterations in expressions of the catalytic subunits p110alpha and p110beta . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
Here we report that insulin causes an increase in wortmannin sensitive PI 3 kinase activity and a gain in the enzyme ' s regulatory and catalytic subunits p85alpha and p110beta ( but not p110alpha ) in the intracellular compartments containing glucose transporters . ^^^ Cytochalasin D also decreased significantly the insulin dependent association of PI 3 kinase activity and the levels of insulin receptor substrate ( IRS ) 1 , p85alpha and p110beta with immunopurified GLUT 4 containing compartments . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
A function for phosphatidylinositol 3 kinase beta ( p85alpha p110beta ) in fibroblasts during mitogenesis : requirement for insulin and lysophosphatidic acid mediated signal transduction . ^^^ In the present study , we have investigated the function of PI 3 Kbeta ( p85alpha p110beta ) during mitogenesis . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
Using subtype specific antibodies , only the PI3K subunits p110beta and p 85 , but not p110alpha and p110gamma , were detected in SW 480 cells . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
In these studies epitope tagged adapter subunit constructs containing wild type p85alpha , p85alpha lacking the SH 3 domain ( deltaSH 3 p85alpha ) , or p85alpha lacking the Rac GAP / BCR homology ( BH ) domain ( deltaBH p85alpha ) were coexpressed with either the p110alpha or p110beta PI 3 kinase catalytic subunit in HEK 293 cells . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
Despite the fact that they bind to the p85alpha regulatory subunit similarly , p110alpha and p110beta appear to have separate functions within cells and to be activated by different stimuli . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
The enzyme exists as a heterodimer containing a regulatory subunit ( e . g . p85alpha ) and one of two widely distributed isoforms of the p 110 catalytic subunit : p110alpha or p110beta . ^^^ When p110alpha and p110beta were overexpressed in 3T3 L 1 adipocytes , exposing cells to insulin induced each of the subunits to form complexes with p85alpha and tyrosine phosphorylated IRS 1 with similar efficiency . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
Comparison of the genomic structure with that of p110alpha , beta , and gamma demonstrates that the p110delta gene shares its exon structure with p110beta , the most closely related PI3K at the amino acid level . . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
METHODS : The effect of BRL 49653 ( Rosiglitazone ) on the mRNA expression of insulin receptor , insulin receptor substrate 1 , p85alpha , p110alpha and p110beta subunits of phosphatidylinositol 3 kinase , Glut 4 and hormone sensitive lipase was examined in isolated adipocytes . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
Indeed , both membrane redistribution and phosphorylation of Gab 1 were reduced in the presence of PI3K inhibitors or dominant negative p110beta . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
In addition , LPA can activate p110beta , a member of the phosphotyrosine dependent PI3K subfamily that participates in the mitogenic effect of LPA . ^^^
Interacting proteins: P42338 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: P42338 and P27986 Pubmed SVM Score :0.0
Western analyses of aortic homogenates revealed the presence of p85alpha , p110alpha , p110beta , and p110delta but not p110gamma PI 3 kinase subunits ; p110delta protein was elevated in aorta of hypertensive rats as compared with sham . ^^^ Aortic homogenates from L NNA rats also had elevated p110beta protein density , but neither L NNA nor DOCA salt had differences in p85alpha and p110alpha . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
Autophosphorylation sites of both PI3K isoforms were mapped to C terminal serine residues of the catalytic p 110 subunit ( i . e . serine 1070 of p 110 beta and serine 1101 of p 110 gamma ) . ^^^ Like other class 1 ( A ) PI3K isoforms , autophosphorylation of p 110 beta resulted in down regulated PI3K beta lipid kinase activity . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
Inducible expression of Galphaq ( Q209L ) in a stably transfected 293 cell line caused a decrease in PI3K activity in p110alpha ( but not p110beta ) immunoprecipitates . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
Small interfering RNA mediated knockdown of the p 110 beta catalytic subunit of PI3K results in a decrease in Delta Np 63 alpha protein levels in keratinocytes . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
However , p 110 beta is far less efficient at phosphorylating p 85 alpha Ser 608 , identifying a potential difference in the mechanisms by which these two isoforms are regulated . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
Runx 2 up regulated PI3K subunits ( p 85 and p110beta ) and Akt , and their expression patterns were similar to that of Runx 2 in growth plates . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
VSMC expressed all class IA PI3K isoforms , but microinjection experiments demonstrated that only the p110beta isoform was involved in chemotaxis . ^^^ In conclusion , glucose sensitizes VSMC to serum , inducing chemotaxis via pathways involving p110beta PI3K , Akt , mTOR , and ERK1 / 2 MAPK . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
RESULTS : Low birthweight subjects showed reduced muscle expression of protein kinase C ( PKC ) zeta , p85alpha , p110beta and GLUT 4 . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
In this study we have defined a key role for the Type Ia phosphoinositide 3 kinase ( PI3K ) p110beta isoform in regulating the formation and stability of integrin alpha ( IIb ) beta ( 3 ) adhesion bonds , necessary for shear activation of platelets . ^^^ Isoform selective PI3K p110beta inhibitors have been developed which prevent formation of stable integrin alpha ( IIb ) beta ( 3 ) adhesion contacts , leading to defective platelet thrombus formation . ^^^ These studies define PI3K p110beta as an important new target for antithrombotic therapy . . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
Of the 8 distinct mammalian isoforms of PI3K , it is the class 1 PI3Ks ( p110alpha , p110beta , p110gamma , and p110delta ) that are responsible for Akt activation . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
Moreover , ATRA increased PI3K activity as well as PI3K catalytic subunit p110beta protein expression , which was completely inhibited by LE 540 treatment . ^^^ Real time polymerase chain reaction analyses demonstrated that ATRA increased PI3K catalytic subunit p110beta mRNA expression without affecting its stability . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
VSM express at least four PI3K isoforms , including the class 1 enzymes p110alpha and p110beta and the class 2 enzymes PI3K C2alpha and C2beta . ^^^ Moreover , KCl and noradrenaline induced stimulation of PI3K C2alpha in a Ca2+ dependent manner , but not of p110alpha or p110beta . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
Mutations in the PIK3CB gene encoding p110beta , the only other widely expressed Class IA PI3K , have not been reported . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
Introduction of a pH 1 vector producing short hairpin RNA that targets a catalytic subunit of PI3K ( p110beta ) also enhanced the TLR mediated responses . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
Finally , analysis of skeletal muscle biopsies showed reduced muscle expression of several key proteins involved in insulin signalling and glucose transport , including protein kinase C zeta , the two subunits of phosphoinositol 3 kinase ( i . e . , p85alpha and p110beta ) and the insulin sensitive glucose transporter , Glut 4 , in individuals of low birth weight . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
Rat neutrophils expressed both class IA PI3K subunits ( p 85 , p110alpha , p110beta , and p110delta ) and a class IB PI3K subunit ( p110gamma ) as assessed by a combination of Western blotting and reverse transcription polymerase chain reaction ( RT PCR ) approaches . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
Platelets express all type 1 PI3K isoforms , including p110alpha , p110beta , p110delta and p110gamma , with recent evidence suggesting important roles for p110gamma and p110beta in regulating distinct phases of the platelet activation process . ^^^ Deficiency of p 110 gamma or inhibition of p110beta produces a marked defect in arterial thrombosis without a corresponding increase in bleeding time , raising the possibility that inhibition of one or more PI3K isoforms may represent an effective antithrombotic approach . . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
Phosphoinositide 3 kinase ( PI3K ) Akt signaling enhances DNA binding of Runx 2 and Runx 2 dependent transcription , and Runx 2 upregulates PI3K subunits ( p 85 and p 110 beta ) and Akt . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
The PIK3CB gene encoding the class 1A PI3K catalytic subunit p110beta was selected as the target of therapeutic approach for malignant gliomas in the present study . ^^^
Interacting proteins: P42338 and P27986 Pubmed SVM Score :0.0
The detection of mRNAs for insulin receptor ( IR ) A and IRB ; insulin receptor substrate ( IRS ) 1 and IRS 2 ; phosphoinositide 3 kinase ( PI3K ) catalytic subunits p110alpha , p110beta , PI3KC2alpha , and PI3KC2gamma ; phosphoinositide dependent protein kinase 1 ; protein kinase B ( PKB ) alpha , PKBbeta , and PKBgamma in the beta cell population suggests the presence of a functional insulin signaling cascade in human beta cells . ^^^
Interacting proteins: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 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: P42338 and P27986 Pubmed SVM Score :0.0
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: P42338 and P27986 Pubmed SVM Score :0.0
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