| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| In addition to p210BCR / ABL and c ABL , p120CBL coprecipitated with an 85 kDa phosphoprotein , which was identified as the p 85 subunit of PI3K . ^^^ These data suggest that BCR / ABL may induce the formation of multimeric complexes of signaling proteins which include p120CBL , PI3K , c CRK or CRKL , c ABL and BCR / ABL itself . . ^^^ |
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| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| When ranked by their discriminating power to separate 37 glioblastomas ( high grade gliomas ) from 45 lower grade gliomas , the following 12 proteins were identified as the most powerful discriminators : IBalpha , EGFRpTyr 845 , AKTpThr 308 , phosphatidylinositol 3 kinase ( PI3K ) , BadpSer 136 , insulin like growth factor binding protein ( IGFBP ) 2 , IGFBP 5 , matrix metalloproteinase 9 ( MMP 9 ) , vascular endothelial growth factor ( VEGF ) , phosphorylated retinoblastoma protein ( pRB ) , Bcl 2 , and c Abl . ^^^ |
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| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| We demonstrate that 5 Abl associates with and stimulates activation of phosphatidylinositol 3 kinase ( PI3K ) and , crucially , that this activation results in enhanced cellular levels of the mass of the second messenger phosphatidylinositol 3 , 4 , 5 trisphosphate . ^^^ |
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| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| Here we report the synthesis and solution structure of the amino terminal SH 3 domain of GRB 2 and of its more stable Ser 32 mutant . 1H NMR analysis of the complex between the Ser 32 GRB 2 N SH 3 domain and the proline rich peptide VPPPVPPRRR , derived from h Sos , shows that relative to the SH 3 peptide complexes described for PI3K , Fyn and Abl , the proline rich peptide in this complex binds in the opposite orientation . . ^^^ |
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| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| Identification of Src , Fyn , Lyn , PI3K and Abl SH 3 domain ligands using phage display libraries . ^^^ We have employed a novel modification of phage display involving biased libraries to identify peptide ligands of the Src , Fyn , Lyn , PI3K and Abl SH 3 domains . ^^^ The Src SH 3 domain prefers the sequence XXXRPLPPLPXP , Fyn prefers XXXRPLPP ( I / L ) PXX , Lyn prefers RXXRPLPPLPXP , PI3K prefers RXXRPLPPLPP while the Abl SH 3 domain selects phage containing the sequence PPPYPPPP ( I / V ) PXX . ^^^ |
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| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| The presence of a type 1 ' turn in the BG loop , which is dependent on the presence of a glycine residue at position BG 3 , is indicative of a binding pocket , characteristic of the Src family , SykC and Abl , rather than a binding groove found in PLC gamma 1C , p 85 alpha N and Shc , for example . . ^^^ |
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| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| Upon treatment with CGP 57148 , CRKL , a specific substrate for BCR ABL that propagates signals via phosphatidylinositol 3 ' kinase ( PI3K ) , was dephosphorylated , indicating inhibition of BCR ABL tyrosine kinase at the cellular level . ^^^ |
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| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| In this study , we demonstrate that BCR / ABL inhibits the expression of a key cell cycle inhibitor , p 27 ( Kip 1 ) , by signaling through a pathway involving phosphatidylinositol 3 kinase ( PI3K ) . p 27 ( Kip 1 ) is a widely expressed inhibitor of cdk 2 , an essential cell cycle kinase regulating entry into S phase . ^^^ The PI3K inhibitor LY 294002 blocks the ability of BCR / ABL to induce p 27 ( Kip 1 ) down regulation and inhibits BCR / ABL induced entry into S phase . ^^^ Overall , these data are consistent with a model in which BCR / ABL suppresses p 27 ( Kip 1 ) protein levels through PI3K / AKT , leading to accelerated entry into S phase . ^^^ This activity is likely to explain in part previous studies showing that activation of PI3K was required for optimum transformation of hematopoietic cells by BCR / ABL in vitro and in vivo . . ^^^ |
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| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| Phosphatidylinositol 3 kinase ( PI3K ) , which has been suggested to associate with and become activated by Bcr Abl , has been shown to be required for Bcr Abl mediated cell growth . ^^^ First , we confirmed that expression of p 185 ( bcr abl ) in HL 60 cells , which renders these cells resistant to apoptosis , induces tyrosine phosphorylation of the p 85 subunit of PI3K . ^^^ Consistent with this result , we observed a 20 fold increase in PI3K activity upon immunoprecipitation of tyrosine phosphorylated proteins from cells expressing Bcr Abl versus control cells . ^^^ Nevertheless , treatment of HL 60 . p185 ( bcr abl ) cells with wortmannin , a potent inhibitor of PI3K , eliminated PI3K activity but did not interfere with the resistance of these cells to apoptosis . ^^^ We conclude that while PI3K participates in the anti apoptotic response mediated by some growth factors and also seems to be important for the growth of Bcr Abl positive cells , it does not play any role in Bcr Abl mediated resistance to apoptosis . . ^^^ |
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| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| Activation of phosphoinositide 3 kinase ( PI3K ) is essential for ABL dependent proliferation and survival in some cell types , and global PI3K inhibitors can enhance the antileukemia effects of the Abl kinase inhibitor imatinib . ^^^ Although a significant fraction of BCR ABL induced human leukemias are of B cell origin , little is known about PI3K signaling mechanisms in B lineage cells transformed by ABL oncogenes . ^^^ Here we show that activation of class 1 ( A ) PI3K and downstream inactivation of FOXO transcription factors are essential for survival of murine pro / pre B cells transformed by 5 ABL or BCR ABL . ^^^ In addition , analysis of mice lacking individual PI3K genes indicates that products of the Pik3r1 gene contribute to transformation efficiency by BCR ABL . ^^^ These findings establish a role for PI3K signaling in B lineage transformation by ABL oncogenes . . ^^^ |
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| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| The designed peptides exhibit a significant increase in the quantum yield of the long wavelength fluorescence emission band ( 596 nm ) upon binding to selected SH 2 domains ( e . g . , Crk SH 2 , Abl SH 2 , and PI3K SH 2 ) . ^^^ |
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| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| Of these , activation of phosphoinositide 3 kinase ( PI3K ) has emerged as one of the essential signaling mechanisms in ABL leukemogenesis . ^^^ |
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| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| We show that the p 85 alpha subunit of PI 3 kinase associates with BCR / ABL and that transient expression of BCR / ABL in fibroblasts and down regulation of BCR / ABL expression using antisense oligodeoxynucleotides ( ODNs ) in Ph 1 cells activates and inhibits , respectively , PI 3 kinase enzymatic activity . ^^^ The use of specific ODNs or antisense constructs to downregulate p 85 alpha expression showed a requirement for p 85 alpha subunit in the proliferation of BCR / ABL dependent cell lines and chronic myelogenous leukemia ( CML ) primary cells . ^^^ The proliferation of two BCR / ABL and growth factor independent cell lines was not affected by downregulation of the expression of the p 85 alpha subunit or inhibition of p 110 enzymatic activity , confirming the specificity of the observed effects on Ph 1 cells . ^^^ |
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| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| Compared to BCR / ABL expressing Ba / F3 cells , BCR / ABL Y177F cells exhibit markedly reduced Gab 2 tyrosine phosphorylation and association of phosphatidylinositol 3 kinase ( PI3K ) and Shp 2 with Gab 2 and BCR / ABL , and decreased PI3K / Akt and Ras / Erk activation , cell proliferation , and spontaneous migration . ^^^ BCR / ABL evoked PI3K / Akt and Ras / Erk activation also are impaired in Gab 2 ( / ) primary myeloid and lymphoid cells . ^^^ |
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| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| The p85alpha subunit of phosphatidylinositol 3 kinase ( PI 3k ) forms a complex with a protein network associated with oncogenic fusion tyrosine kinases ( FTKs ) such as BCR / ABL , TEL / ABL , TEL / JAK2 , TEL / PDGFbetaR , and NPM / ALK , resulting in constitutive activation of the p 110 catalytic subunit of PI 3k . ^^^ Introduction of point mutations in the N terminal and C terminal SH 2 domain and SH 3 domain of p85alpha , which disrupt their ability to bind phosphotyrosine and proline rich motifs , respectively , abrogated their interaction with the BCR / ABL protein network . ^^^ The p85alpha mutant protein ( p85mut ) bearing these mutations was unable to interact with BCR / ABL and other FTKs , while its binding to the p110alpha catalytic subunit of PI 3k was intact . ^^^ |
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| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| Here , we demonstrate that IM treatment activated the phosphatidylinositol 3 kinase ( PI3K ) / Akt / mammalian target of rapamycin ( mTor ) pathway in BCR / ABL positive LAMA cells and primary leukemia cells in vitro , as well as in a chronic phase CML patient in vivo . ^^^ In fact , PI3K / Akt activation critically mediated survival during the early phase of IM resistance development before manifestation of BCR / ABL dependent strong IM resistance such as through a kinase mutation . ^^^ |
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| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| We show that a signaling protein , phosphatidylinositol 3 kinase ( PI 3k ) , is essential for growth of CML cells , but not of normal hematopoietic cells , and that p85alpha subunit of PI 3k co immunoprecipitates with BCR / ABL . ^^^ Therefore , we made an attempt to better characterize p85alpha BCR / ABL interactions . ^^^ Pull down and Western analyses were performed to detect the interaction between BCR / ABL and p85alpha SH 3 . ^^^ BCR / ABL transformed 32Dcl3 cells were infected with internal ribosome entry site green fluorescent protein retroviral construct encoding p85alpha SH 3 mutants to assess their biological effects . ^^^ The interaction between p85alpha SH 3 and BCR / ABL may be intermediated by proteins such as c Cbl , Shc , Grb 2 , and / or Gab 2 . ^^^ |
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| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| Among the major pathways activated by BCR / ABL that regulate translation , PI3K and mammalian target of rapamycin were shown to control MICA expression . ^^^ |
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| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P00519 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|