| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.5050721 |
| ARIA stimulated association of PI3K with erbB 3 , expression of an activated PI3K led to ARIA independent AChR epsilon subunit expression , and inhibition of PI3K abolished the action of ARIA . 0.5050721^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Ligand caused p 120 rasGTPase activating protein ( GAP ) , SHC and the p 85 subunit of phosphatidylinositol 3 ' kinase ( PI3K ) to be associated with both p185c erbB 2 and p180erbB 4 . ^^^ Furthermore , comparative analysis of the binding of p 85 PI3K to 185c erbB 2 and p180erbB 4 , revealed a preferential association with activated p180erbB 4 . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| In addition , the G ( 1 ) arrest and up regulation of p 27 resulting from EGFR blockade are not due to the interruption of MAPK , but to the interruption of constitutively active PI3K function . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Furthermore , erbB 3 principally mediated the direct recruitment of p 85 in cells stimulated by HRG or EGF , indicating that , in addition to the high level activation of PI3K by p 185 ( erbB 2 ) / erbB 3 , EGFR / erbB 3 heterodimer interaction is essential for the weak but significant level of PI3K activated by EGF in cells that express normal EGFR levels . ^^^ Phosphatidylinositol 3 kinase ( PI3K ) is activated by p 185 ( erbB 2 ) / erbB 3 heterodimers in cells stimulated by HRG , and PI3K is constitutively activated by p 185 ( erbB 2 ) / erbB 3 in breast carcinoma cells that overexpress c erbB 2 . ^^^ To better understand the relative abilities of HRGs , epidermal growth factor ( EGF ) , or insulin to activate PI3K under normal physiological conditions , we compared the levels of recruitment of the 85 kDa regulatory subunit of PI3K when activated by the type 1 ( erbB ) or type 2 [ insulin like growth factor ( IGF ) ] receptor tyrosine kinases in two different nontransformed human mammary epithelial cell lines . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| The mechanism by which EGFR recruits the PI3K / Akt pathway was in part differentially regulated at the level of Ras but independent of heterodimerization of EGFR with either ErbB 2 or ErbB 3 based upon functional dissection of pathways in esophageal cancer cell lines . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| While investigating the downstream signals involved in HRG beta 1 enhanced cell aggregation , we observed that HRG beta 1 induced tyrosine phosphorylation of erbB 2 and crbB 3 receptor heterodimers and increased the association of the dimerized receptors with the 85 kDa subunit of phosphatidylinositol 3 kinase ( PI3K ) . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Apoptosis induced by PI3K inhibition was attenuated by : ( a ) dihydrotestosterone ; or ( b ) the ErbB 1 activating ligands [ epidermal growth factor ( EGF ) , transforming growth factor alpha , or heparin binding EGF like growth factor ] . ^^^ In response to ErbB 1 activation by ligand , the p 85 regulatory subunit of PI3K associated specifically with ErbB 3 but not detectably with ErbB 1 . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Finally , we show that LPA can not activate PI3K in cell lines lacking the EGFR / Gab1 pathway , including cells that transactivate the PDGF receptor . ^^^ Altogether , these results demonstrate that activation of PI3K by LPA is conditioned by the ability of LPA to transactivate an EGFR / Gab1 signaling pathway . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Taken together these results suggest that coexpression of SCF and Kit may enhance responsiveness to erbB ligands by enhancing activation of the MAPK and PI3K pathways . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Upregulation of VEGF and angiogenesis can also be induced by constitutive activation of other oncogenic proteins ( e . g . , EGFR , Raf , MEK , PI3K ) acting at various levels on the Ras signaling pathway . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| AVP appeared to exert its effect on MAPK and PI3K activation , as well as on cell proliferation , by activating the epidermal growth factor receptor ( EGF R ) . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Pretreatment of endothelial cells with AG 1478 , an inhibitor of the ErbB receptor family , resulted in the suppression of PI3K activation by arachidonic acid . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| TRH activation of MAPK required PKC but was insensitive to pertussis toxin and did not require ras , epidermal growth factor receptor kinase , or PI3K . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Treatment with AG 1478 resulted in rapid ErbB 2 dephosphorylation , reversible G ( 1 ) arrest , and interruption of constitutive mitogen activated protein kinase ( MAPK ) and phosphatidylinositol 3 kinase ( PI3K ) / Akt signaling . ^^^ These data imply that : ( a ) modulation of both p 27 and cyclin D 1 are required for the growth arrest that results from blockade of the ErbB 2 kinase ; and ( b ) ErbB 2 overexpressing cells use both MAPK and PI3K / Akt to modulate p 27 and cyclin D 1 and , hence , subvert the G ( 1 ) to S transition . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| In this report , we demonstrate that addition of the PI3K reaction products does not suppress wortmannin induced enlargement of EGFR containing endosomes and enhancement of EGFR degradation . ^^^ We conclude that wortmannin alters intracellular trafficking of EGFR by activating Rab 5 rather than by inhibiting PI3K . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| We found that EGF stimulation and EGFR oncoprotein ( DeltaEGFR ) expression independently induced the co immunoprecipitation of the p 85 subunit of PI3K with SHP 2 . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Phosphatidylinositol 3 kinase ( PI3K ) and ERK1 / 2 mitogen activated protein kinase ( ERK1 / 2 MAPK ) , two signal molecules downstream of the EGFR , have been recognized as participants in two survival signal pathways in response to stress . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Induction of cellular stress resulted in complex formation between PI3K and ErbB2 / ErbB3 and enhanced PI3K activity , implicating ErbB proteins as downstream effectors of stress induced insulin resistance . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| However , in this report we demonstrate that inhibition of epidermal growth factor ( EGF ) stimulated PI3K activity by expression of the kinase deficient PI3K p 110 subunit ( p110delta kin ) does not block the lysosomal targeting and degradation of the EGF receptor ( EGFR ) . ^^^ Moreover , inhibition of total PI3K activity by wortmannin or LY 294002 significantly enlarges EGFR containing endosomes and dissociates the early endosomal autoantigen EEA 1 from membrane fractions . ^^^ The present work suggests that the intracellular trafficking of EGFR is controlled by a novel endosome fusion pathway that is regulated by Rab 5 in the absence of PI3K , rather than by the previously defined endosome fusion pathway that is co regulated by Rab 5 and PI3K . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| ERK activation through both TPalpha and TPbeta was dependent on PKA and phosphoinositide 3 kinase ( PI3K ) class 1 ( A ) , but not class 1 ( B ) , and was modulated by Harvey Ras , A Raf , c Raf , and Rap1B / B Raf and also involved transactivation of the epidermal growth factor receptor . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| EGFR can activate the phosphotidylinositol 3 kinase ( PI3K ) and mitogen activated / extracellular signal regulated kinase ( MEK ) pathways , which can potentially modulate activation of NF kappaB and AP 1 , respectively . ^^^ In our study , we examined the effect of EGF and antagonists of EGFR , PI3K and MEK on NF kappaB and AP 1 activation and IL 8 and VEGF expression in HNSCC cell lines UM SCC 9 and 11B in which EGFR is overexpressed and activated . ^^^ EGFR , PI3K and MEK antagonists inhibited growth of HNSCC . ^^^ We conclude that antagonists of EGFR , PI3K and MEK signal pathways have inhibitory activity against EGFR induced NF kappaB and AP 1 activation , IL 8 and VEGF expression and growth by HNSCC . ^^^ Effects of pharmacologic antagonists of epidermal growth factor receptor , PI3K and MEK signal kinases on NF kappaB and AP 1 activation and IL 8 and VEGF expression in human head and neck squamous cell carcinoma lines . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| In both MKN 7 and BT 474 tumor cells , the degree of ligand induced rescue from the inhibitors correlated with the potency of ErbB receptor activation and stimulation of the PI3K and MAPK intracellular signaling pathways . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| EGFR dependent Erb B 3 signaling also contributed to p 70 S6 kinase activity through recruitment and activation of PI3K , which has been shown to regulate p 70 S6 kinase activity . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| By comparing these two ligands and the use of specific inhibitors for phosphatidylinositol 3 kinase ( PI3K ) , mitogen activated protein kinase ( MAPK ) and p38MAPK , we have identified several molecular mechanisms required for ErbB receptor mediated proliferation . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| All of the cell lines expressing EGFR responded to epidermal growth factor ( EGF ) by activation of the downstream signaling pathways , mitogen activated protein ( MAP ) / extracellular signal regulated kinase kinase / MAP kinase , and phosphatidylinositol 3 ' kinase ( PI3k ) / AKT . ^^^ We conclude that EGFR expression is a common feature of the Nf 1 : p 53 tumor cell lines and that inhibition of this molecule or its downstream target PI3k , may be useful in the treatment of NF 1 related malignancies . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| The epidermal growth factor receptor ( EGFR ) is frequently amplified in this disease ( < or=80 % ) and can lead to activation of phosphatidylinositol 3 kinase ( PI3K ) , both directly and indirectly through Ras . ^^^ Radiation survival was determined in the SQ20B cell line , a radioresistant squamous cell line derived from a recurrent laryngeal cancer , after pharmacological blockade of EGFR with Iressa , of Ras by the FTI L 744 , 832 , or of PI3K by LY 294002 . ^^^ Pharmacologically inhibiting EGFR , Ras , and PI3K led to radiosensitization of SQ20B cells . ^^^ These results also suggest that signaling from EGFR to PI3K can lead to radioresistance . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| In contrast , inhibition of phosphatidylinositol 3 kinase ( PI3K ) blocked the constitutive phosphorylation of Erk and AKT 1 but not the EGFR . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Some stress induced signaling pathways are those normally activated by mitogens such as the EGFR / RAS / PI3K MAPK pathway . ^^^ This includes radiation induced signaling via the EGFR and IGFI R to the PI3K , MAPK , JNK , and p 38 pathways as well as FAS R and TNF R signaling to pro caspases and NFKB . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| These results show a nonredundant function of PI3K isoforms downstream of the epidermal growth factor receptor and indicate that the presence of p110delta may confer breast cancer cells with selective migratory capacities . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| In the present study , we examined heregulin ( HRG ) induced signal transduction of ErbB 4 receptor and found that the phosphatidylinositol 3 ' kinase ( PI3K ) Akt pathway negatively regulated the extracellular signal regulated kinase ( ERK ) cascade by phosphorylating Raf 1 on Ser ( 259 ) . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Thus , in EGFR expressing tumor cells with concomitant amplification ( s ) of PI3K Akt signaling , combined blockade of the EGFR tyrosine kinase and Akt should be considered as a therapeutic approach . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| By contrast , an inhibitor of epidermal growth factor receptor kinase , AG 1478 , which prevents carbachol stimulated ErbB 3 transactivation , PI3K recruitment and protein kinase B activation in 1321N1 cells , reduced activation of S6K1 by no more than 30 % . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| We conclude that cholesterol depletion from the plasma membrane by MbetaCD causes ligand independent activation of EGFR , resulting in MAPK activation by PI3K and Ras dependent mechanisms . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Accordingly , T47D cells grown on LAM had the greatest increase in ErbB 2 activation , PI3K activity , and phosphorylation of Akt . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| The effect of EGFR activation on VEGF was mediated at the level of transcription via a phosphatidylinositol 3 ' kinase ( PI3K ) dependent pathway . ^^^ Therefore , in human glioblastoma cells , PTEN mutation can cooperate with EGFR activation to increase VEGF mRNA levels by transcriptionally up regulating the proximal VEGF promoter via the PI3K / Akt pathway . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Expression of the mutant epidermal growth factor receptor 8 is also tightly correlated with phosphorylation of these effectors , demonstrating an additional route to PI3K pathway activation in glioblastomas in vivo . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Multiple genetic alterations such as in Ras or EGFR can result in sustained signaling through PI3K . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Moreover , these data are strengthened by in vitro studies showing that inhibition of EGFR , Ras , PI3K , and Akt radiosensitized cancer cell lines . ^^^ We now suggest that EGFR , which is upstream of PI3K , may also mediate resistance through a common pathway . ^^^ In addition to EGFR and Ras , PTEN can also regulate the PI3K pathway . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| In breast cancer cells , PI3K / Akt and mTOR pathways seem to be critical for the proliferative responses mediated by the epidermal growth factor receptor , the insulin growth factor receptor , and the estrogen receptor . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Our results point to the involvement of several ErbB specific ligands ( amphiregulin and neuregulin 1 ) and enzymes or adaptor molecules ( PI3K , Src , Shc and Grb 7 ) in the ErbB pathway dysregulation associated with breast cancer . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Moreover , these data are strengthened by in vitro studies showing that inhibition of EGFR , RAS , PI3K , and AKT radiosensitized cancer cell lines . ^^^ We now suggest that EGFR , which is upstream of PI3K , may also mediate resistance through a common pathway . ^^^ In addition to EGFR and RAS , PTEN can also regulate the PI3K pathway . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| UV ( 50 mJ / cm2 from UVB source ) irradiation caused rapid recruitment of PI3K to the epidermal growth factor receptor ( EGFR ) . ^^^ Pretreatment of KCs with EGFR inhibitor PD 169540 abolished UV induced Akt activation / phosphorylation , as did the PI3K inhibitors LY 294002 or wortmannin . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| We show here that pharmacologic down regulation of constitutive PI3K / Akt pathway signaling using the PI3K inhibitor LY 294002 similarly restores EGFR stimulated Akt signaling and sensitizes MDA 468 cells to ZD 1839 . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Here , we demonstrate Delta Np 63 alpha is a target of the phosphoinositide 3 kinase ( PI3K ) pathway downstream of the epidermal growth factor receptor . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Analysis of genes encoding proteins that may activate the pathway upstream of Pi3k revealed variable fractions of tumors with EGFR amplification ( 31 % ) , PDGFRA amplification ( 8 % ) , and IRS 2 amplification ( 2 % ) . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| VIP and Bt2cAMP / AM both stimulated ERK MAPK phosphorylation and recruitment of the p 85 subunit of phosphatidylinositol 3 kinase ( PI3K ) to the EGFr in a tyrphostin AG 1478 sensitive manner . ^^^ Through a mechanism that likely involves PI3K , transactivation of the EGFr is required for the full expression of cAMP dependent Cl secretory responses . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| A link between EGFR , phosphatidylinositide 3 kinase ( PI3K ) and hyposmotically induced taurine ( but not 86Rb ) release is suggested by the increase in PI3K activity elicited by hyposmolarity , which was fully prevented by EGFR inhibition , and by a marked reduction of hyposmotically induced taurine ( but not 86Rb ) release , by wortmannin . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Our results also demonstrate that the PI3K signaling pathway is an integral component of the overall signaling network induced by growth in 3D , as reversion affected by inhibition of PI3K signaling also down modulates the endogenous levels of beta 1 integrin and epidermal growth factor receptor , the upstream modulators of PI3K , and up regulates PTEN , the antagonist of PI3K . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Combined inhibition of phosphatidylinositol 3 ' kinase ( PI3K ) and extracellular signal regulated kinase 1 / 2 ( ERK1 / 2 ) mimicked the protective effects of EGFR inhibition on hypoxia induced cell death and protein S 6 dephosphorylation . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Anti ErbB 2 monoclonal antibody 2C4 blocked heregulin stimulated phosphorylation of ErbB 2 and ErbB 3 ; activation of mitogen activated protein kinase ( MAPK ) , phosphatidylinositol 3 ' kinase ( PI3K ) , and Akt ; proliferation ; and anchorage independent growth . 2C4 blocked EGF mediated phosphorylation of ErbB 2 and inhibited PI3K / Akt and anchorage independent growth but did not affect ErbB 1 or MAPK . ^^^ Immunoprecipitations showed that ErbB 3 and Grb 2 associated binder ( Gab ) 1 were phosphorylated and associated with PI3K activity after heregulin treatment and that Gab 1 and Gab 2 , but not ErbB 3 , were phosphorylated and associated with PI3K activity after EGF treatment . ^^^ Furthermore , we identify ErbB 2 as a critical component of EGF signaling to the Gab1 / Gab2 PI3K Akt pathway and anchorage independent growth , but EGF stimulation of MAPK and monolayer growth can occur efficiently without the contribution of ErbB2 . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| We then examined the effects of the PI3K inhibitor LY 294002 , MEK inhibitor U 0126 , and the epidermal growth factor receptor tyrosine kinase inhibitor PKI 166 on these signaling pathways and induction of apoptosis . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Using sublingual gland acinar cells , we show that prosecretory effect of isoproterenol on phospholipid release was subjected to suppression by EGFR kinase inhibitor , PD 153035 , and wortmannin , an inhibitor of PI3K , but not by PD 98059 , an inhibitor of extracellular signal regulated kinase ( ERK ) . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| To inhibit the pathways selectively , 3 specific kinase inhibitors , AG 1478 ( an inhibitor of EGFR ) , PD 98059 ( an inhibitor of MEK ) and LY 294002 ( an inhibitor of PI3K ) , were combined with radiation . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| In many cell types PI3K / AKT signaling is a key cytoprotective response downstream of the EGFR family receptors and mediated carcinogenesis . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| The impedance by ciglitazone of the LPS induced reduction in mucin synthesis was countered ( up to 68 . 9 % ) in a dose dependent fashion by a specific inhibitor of EGFR kinase , PD 153035 , as well as wortmannin , an inhibitor of phosphatidylinositol 3 kinase ( PI3K ) . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| The BTC dependent activation of JNK and PI3K / Akt pathways occurred predominantly via EGFR , whereas activation of the MEK 1 / ERK pathway occurred via all 4 c erbB receptors , although again predominantly via EGFR . ^^^ Taken together , our data show that BTC induces MMP 9 production and invasion primarily through activation of EGFR , MAPK and PI3K / Akt in HNSCC cells . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Phosphoinositide 3 kinase ( PI3K ) , tyrosine kinase of the epidermal growth factor receptor ( EGFR ) , and mitogen activated protein kinase kinases ( MEK ) inhibitors were also tested . ^^^ The results suggest that EGFR , PI3K , and ERK are required for the proliferative effects of BK . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| In addition , EGF stimulated PI3K activity , a key signalling pathway for invasion of these cells , was decreased in PC 3 AR cells and further reduced by treatment with R 1881 , indicating decreased functionality of EGFR . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| In tumor cells , the PI3K / Akt pathway is induced through activation of members of ErbB receptor tyrosine kinases . ^^^ The integrity of both the ErbB and the vascular endothelial growth factor ( VEGF ) ligand activated PI3K / Akt pathway in endothelial cells was demonstrated using specific ErbB and VEGF receptor tyrosine kinase inhibitors . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
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 . ^^^ Increased activation of the EGFR PI3K Akt signaling pathway in tumors relative to Apc+ / + and ApcMin / + enterocytes provides potential opportunities for therapeutic interventions to differentially suppress tumor formation , promotion , progression , and / or recurrence . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Accumulated evidence indicates that overexpression of epidermal growth factor receptor and HER2 / neu , which occurs frequently in NSCLC , leads to the deregulation of PI3K and MAPK , activating Akt and enhancing chemoresistance . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| EGFR , Akt [ a target of phosphoinositide 3 kinase ( PI3K ) ] , and ERK1 / 2 were activated after plating and mechanical injury , and their phosphorylation was further enhanced by addition of exogenous EGF . ^^^ These results show that EGFR activation is required for RPTC proliferation and migration and that proliferation is mediated by PI3K , whereas migration is mediated by p38 . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| METHODS : Epithelial monolayers of a telomerase immortalized HCEC line , HUCL , and primary culture of HCECs were infected with Pseudomonas aeruginosa in the presence of the EGFR inhibitor tyrphostin AG 1478 , the extracellular signal regulated kinase ( ERK ) inhibitor U 0126 , the phosphoinositide 3 kinase ( PI3K ) inhibitor LY 294002 , the heparin binding EGF like growth factor ( HB EGF ) antagonist CRM 197 , the HB EGF neutralizing antibody , or the matrix metalloproteinase inhibitor GM 6001 . ^^^ RESULTS : P . aeruginosa infection of HUCL cells resulted in EGFR activation and EGFR dependent ERK1 / 2 and PI3K phosphorylation . ^^^ Inhibition of EGFR , ERK1 / 2 , and PI3K activities with kinase specific inhibitors ( AG 1478 , U 0126 , and LY 294002 , respectively ) resulted in an increase in the number of apoptotic cells , in elevated cellular caspase 3 activity , and / or in increased cleaved PARP in P . aeruginosa infected HUCL cells or primary culture of HCECs . ^^^ EGFR and its downstream ERK and PI3K signaling pathways play a role in preventing epithelial apoptosis in the early stage of bacterial infection . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Using [ 14C ] choline labeled gastric mucosal cells in culture , we show that stimulatory effect of beta adrenergic agonist , isoproterenol , on phospholipid release was subject to a dose dependent suppression by EGFR kinase inhibitor , PD 153035 , as well as wortmannin , a specific inhibitor of PI3K . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Given that many glioma tumors show deregulation of the PI3K signaling pathway , either through loss of the tumor suppressor protein PTEN or overexpression of the growth factor EGFR , the ability to identify different subsets of patients using simple immunohistochemistry for the presence of absence of pAkt could enable selection of the appropriate kinase inhibitor , such as GA , for drug therapy . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
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: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| A number of genetic alterations are associated with this disease including mutations and amplifications of EGFR ( 70 % ) and Ras ( 20 30 % ) , both of which are upstream of PI3K . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Using [ ( 3 ) H ] glucosamine labeled mucous acinar cells of sublingual salivary gland in culture , we show that stimulatory effect of beta adrenergic agonist , isoproterenol , on mucin secretion was inhibited in a concentration dependent manner by EGFR kinase inhibitor , PD 153035 , as well as wortmannin , an inhibitor of PI3K . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Although hypoxia is a potent inducer of VEGF , we previously showed that epidermal growth factor receptor amplification and loss of PTEN , both of which can increase phosphatidylinositol 3 kinase ( PI3K ) activity , increase VEGF expression . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Using immunoprecipitation assays , we showed that the neuregulin 1beta1 ( NRG1beta1 ) stimulus induced ErbB 4 tyrosine phosphorylation and phosphatidylinositol 3 kinase ( PI3K ) recruitment and activation ( as demonstrated by Akt phosphorylation ) either directly ( ErbB 4 cyt1 isoform ) or indirectly ( ErbB 4 cyt2 isoform ) . ^^^ Our data show that ErbB 4 signaling via PI3K activation plays a fundamental role in controlling NRG1beta1 induced migration . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| To determine the importance of these signal transduction pathways , the conditionally transformed hematopoietic cells were treated with EGF R , PI3K and MEK inhibitors . ^^^ However , MEK and PI3K inhibitors only induced apoptosis at 1000 fold higher concentrations than the EGFR inhibitor . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Expression of 5R affected both the intensity and the duration of wound induced , EGFR elicited ERK and PI3K activation . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Met 5 enkephalin induced cardioprotection occurs via transactivation of EGFR and activation of PI3K . ^^^ We conclude that ME induced cardioprotection is mediated via Src dependent EGFR transactivation and activation of the PI3K and MAPK pathways . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| DIM also inhibited EGFR expression , PI3K kinase activity , and Akt activation , and abrogated the EGF induced activation of PI3K in prostate cancer cells . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Moreover , alpha6beta4 associated haptotaxis inhibition was linked to a phosphatidylinositol 3 kinase ( PI3K ) pathway and required erbB 2 activation . erbB 2 , the ligand less member of the epidermal growth factor receptor family , was shown to form a complex with the hemidesmosomal integrin alpha6beta4 . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| We investigated whether the presence of the androgen receptor could affect EGFR mediated signaling by evaluating autotransphosphorylation of the receptor as well as activation of the downstream signaling pathway PI3K / AKT . ^^^ In addition , EGF stimulated PI3K activity , a key signaling pathway for invasion of these cells , was decreased in PC 3 AR cells and further reduced by treatment with R 1881 , indicating decreased functionality of EGFR . ^^^ We demonstrate that in the androgen insensitive cell lines PC 3 and DU 145 this compound was able to decrease in vitro invasion of Matrigel by inhibiting EGFR autotransphosphorylation and subsequent PI3K activation . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Pretreatment of cells with inhibitors of PI3K , Src family tyrosine kinases , and EGFR also decreased HUVEC migration . ^^^ In conclusion , these results suggest that Ang 2 mediates an increase in FAK and paxillin phosphorylation and induces HUVEC migration through signal transduction pathways dependent on PI3K and Src tyrosine kinase activation and EGFR transactivation . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| The EGF receptor ( EGFR ) has been reported to activate both MEK and PI3K . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| In conclusion , data indicate that the P2Y2 induced phosphorylation of ERK1 / 2 and the induction of c Fos are due to the operation of CaM , with PKC , PI3K , EGFR and receptor endocytosis mechanisms endorsing the signalling . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Two gefitinib sensitive NSCLC cell lines with endogenous distinct activating EGFR mutations ( L858R and Del 747 749 ) , frequently observed in NSCLC patients who respond to gefitinib , also use ErbB 3 to couple to PI3K . ^^^ We conclude that ErbB 3 is used to couple EGFR to the PI3K / Akt pathway in gefitinib sensitive NSCLC cell lines harboring WT and mutant EGFRs . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Inhibition of EGFR , ERK1 / 2 and PI3K blocked neuroblastoma differentiation after serum withdrawal . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Phosphatidylinositol 3 ' kinase ( PI3K ) / Akt and Ras / Raf / mitogen activated protein kinase ( MAPK ) , the two main EGFR signaling pathways , mediate EGFR effects on proliferation and survival . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| This enhancement is due to an increase in cell survival rather than an increase in cell proliferation and is dependent on the activation of erbB 2 and phosphatidylinositol 3 kinase ( PI3K ) . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Neuregulin induced activation of CDK 2 also depended on the ErbB receptor , MAPK , and PI3K , all of which have previously been shown to be required for AChRepsilon expression . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| These assays were repeated in the presence of the Galphai inhibitor pertussis toxin ( PTx , 100 ng / mL ) , the Ras inhibitor manumycin A ( MA , 10 microM ) , the phosphatidyl inositol 3 ' kinase ( PI3K ) inhibitor wortmannin ( WN , 1 microM ) , the EGFR inhibitor AG 1478 ( AG , 10 nM ) , the MEK 1 inhibitor PD 98059 ( PD , 10 microM ) , the p 38 MAPK inhibitor SB 203580 ( SB , 10 microM ) , and the plasmin inhibitors aprotinin and epsilon aminocaproic acid . ^^^ In contrast , activation of MKK3 / 6 was abrogated by inhibition of Galphai , but not by Ras or PI3K inhibition . uPA induced time dependent phosphorylation of EGFR , which was dependent on plasmin activity . ^^^ Inhibition of EGFR reduced both ERK1 / 2 and p 38 MAPK activation . uPA activation of PI3K and MKK3 / 6 was EGFR dependent and that of MEK 1 was EGFR independent . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| In fact , the inhibition of PI3K blocked the EGF induced invasiveness in PTEN positive cells but not in PTEN negative cells , in which PI3K activity was not influenced by EGFR / Her2 activation , whereas the inhibition of MAPK was able to block the invasive phenomena in both cell types . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Anti inflammatory effects of pharmacological agents targeted at tyrosine kinases , Syk , Itk , signal transducer and activator of transcription 1 , NF kappaB , GATA 3 , EGFR , PI3K , MEK1 / 2 , p 38 MAPK and JNK have been reported in animal models of allergic airway inflammation . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| In summary , our results identify ErbB 3 and the downstream PI3K Akt pathway as important determinants of the cytotoxic activity of KF in vitro . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Phosphoinositide 3 kinase ( PI3K ) is one of the important cell survival signaling molecules activated by EGF R stimulation . ^^^ However , the extent to which EGF R transactivation is essential for GPCR agonist stimulated PI3K activation is not known . ^^^ Here we examined the mechanism of PI3K activation that elicits GPCR mediated ERK1 / 2 activation by pathways dependent and / or independent of EGF R transactivation in specific cell types . ^^^ Immortalized hypothalamic neurons ( GT 1 7 cells ) express endogenous gonadotropin releasing hormone receptors ( GnRH R ) and their stimulation causes marked phosphorylation of ERK1 / 2 and Akt ( Ser 473 ) through transactivation of the EGF R and recruitment of PI3K . ^^^ In C 9 hepatocytes , agonist activation of AT 1 angiotensin 2 ( AT 1 R ) , lysophosphatidic acid ( LPA ) , and EGF receptors caused phosphorylation of Akt through activation of the EGF R in a PI3K dependent manner . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Further , FSH and LH significantly increased activities of various kinases at 5 10 min , and pre treatments with LY 294002 ( an inhibitor of PI3K ) or PD 98059 ( an inhibitor of ERK1 / 2 ) partially blocked the gonadotropin induced up regulation of EGFR in IOSE 80PC cells . ^^^ Taken together , these results suggest that the effect of gonadotropins on the expression of EGFR may affect cell growth via ERK 1 / 2 and PI3K pathways in pre neoplastic ovarian surface epithelial cells , and that FSH and LH increase EGFR mRNA by different mechanisms . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Independent role of phosphoinositol 3 kinase ( PI3K ) and casein kinase 2 ( CK 2 ) in EGFR and Her 2 mediated constitutive NF kappaB activation in prostate cancer cells . ^^^ EGFR activates NF kappaB through the PI3K / Akt pathway that leads to the phosphorylation of IkappaBalpha on serines 32 and 36 , thereby promoting the nuclear translocation of the p 65 subunit . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Papilloma cells overexpress the EGFR and have constitutively active extracellular signal regulated kinase ( ERK ) and enhanced phosphatidylinositol 3 kinase ( PI3K ) activity , but overexpression of the lipid phosphatase PTEN ( Phosphatase and Tensin Homolog ) reduces activation of Akt by PI3K . ^^^ We hypothesized that the altered differentiation of papillomas reflects these changes in signaling from the EGFR ERK and PI3K Akt pathways and that one or both of these pathways is required for the normal differentiation process in mucosal epithelium . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Mechanistically , the activation of the PI3K / Akt pathway in keratinocyte differentiation depends on the activity of the epidermal growth factor receptor and Src families of tyrosine kinases and the engagement of E cadherin mediated adhesion . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| In many human lung adenocarcinoma cell lines , a pathway involving epidermal growth factor receptor ( EGFR ) , ErbB 2 and ErbB 3 receptors , phosphatidyl inositol 3 kinase ( PI3K ) , Akt , glycogen synthase kinase 3 beta ( GSK 3 beta ) , and cyclin D 1 controls cell growth , survival , and invasiveness . ^^^ The effector pathway from the EGFR to PI3K in these nontransformed cells included the adaptor Grb 2 , the docking protein Gab 1 , and the phosphatase Shp 2 . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| However , the PI3K inhibitors do not show inhibitory effects on p 38 , Src , and EGFR . ^^^ These data suggest that p 38 and EGFR kinase mediated Akt activation is required for Zn2+ induced COX 2 expression and that the PI3K / Akt signaling pathway plays a central role in this event . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Using [ ( 3 ) H ] glucosamine labeled gastric mucosal cells , we show that stimulatory effect of beta adrenergic agonist , isoproterenol , on mucin secretion was inhibited by EGFR kinase inhibitor , PD 153035 , as well as wortmannin , a specific inhibitor of PI3K . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Given the accumulating clinical evidence of the activity of anti EGFR agents in GBM and the preclinical data suggesting the important role of downstream mediators as effectors of EGFR signaling , the RTOG is conducting additional investigations into the prognostic value of activation patterns of EGFR signaling , both at the level of the receptor ( e . g . , EGFRvIII , phospho EGFR ) and at the level of downstream signal transduction pathways ( e . g . , PI3K , Ras / MAPK pathways ) . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Gefitinib resistant NSCLC cell lines , showing EGFR independent activity of the PI3K / Akt or Ras / Erk pathways , were treated with gefitinib in combination with specific inhibitors of mTOR , P13K , Ras , and MEK . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| PI3K AKT pathway negatively controls EGFR dependent DNA binding activity of Stat 3 in glioblastoma multiforme cells . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Glioblastomas frequently carry genetic alterations resulting in an aberrant activation of the phosphoinositol 3 kinase ( Pi3k ) / protein kinase B ( Akt ) signalling pathway , including most notably phosphatase and tensin homolog ( PTEN ) mutation , epidermal growth factor receptor ( EGFR ) amplification and rearrangement , as well as carboxyl terminal modulator protein ( CTMP ) hypermethylation [ Knobbe et al . , ( 2004 ) Hypermethylation and transcriptional downregulation of the carboxyl terminal modulator protein gene in glioblastomas . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Both the PI3K / Akt and p 38 MAPK pathways are activated in a Src family kinase dependent fashion on EGF R activation and are important for EGF mediated VEGF production in pancreatic cancer cells . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Notably , activation of the PI3K downstream mediator PKB / Akt by GPCR ligands involves the activity of sphingosine kinase ( SPHK ) and is independent of EGFR signal transactivation . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| We demonstrate that increased expression of EGFR enhanced its association with PI3K C2beta following stimulation with EGF . ^^^ Deletion of the first proline rich region within the N terminus precluded recruitment of PI3K C2beta to activated EGFR . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Blocking of ErbB 1 , phosphatidylinositol 3 kinase ( PI3K ) / Akt , or mitogen activated protein kinase / ERK kinase ( MEK ) / ERK activity resulted in significant reduction in intrinsic and HB EGF induced restitution in vitro . ^^^ CONCLUSIONS : Endogenous HB EGF , ErbB 1 , PI3K / Akt , and MEK / ERK are involved in intrinsic restitution . rHB EGF enhances restitution in vivo and in vitro in a PI3K / Akt and MEK / ERK1 / 2 dependent fashion . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| This apoptosis is further enhanced by phosphatidylinositol 3 kinase ( PI3K ) inhibitor ( LY 294002 ) , but not by MEK1 / 2 inhibitor ( U 0126 ) , indicating the strong dependency of their survival on PI3K / Akt pathway rather than MAPK pathway , the major downstream signaling pathways of EGFR . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Therapeutic maneuvers may target receptor tyrosine kinases ( EGFR , VEGFR , FGFR ) , chemokines or G protein coupled receptors ( CXCR 4 , CXCR 2 , EphB 2 ) , hypoxia inducible factor ( HIF ) , and signaling pathways ( c Src , PI3K , Akt , chaperon complexes ) in tumor cells . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Together these observations suggest that thrombin induces both VSMC DNA synthesis and motility via EGFR dependent stimulation of PI3K / Akt signaling targeting in parallel the Fra 1 mediated FGF 2 expression and mTOR S6K1 activation . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| The BAD protein integrates survival signaling by EGFR / MAPK and PI3K / Akt kinase pathways in PTEN deficient tumor cells . ^^^ Serine 112 phosphorylation is EGFR / MEK / MAPK dependent , whereas serine 136 phosphorylation is PI3K / Akt dependent . ^^^ Combined inhibition of EGFR and PI3K signaling may be a useful therapeutic strategy . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| The human epidermal growth factor receptor 2 ( HER 2 ) protein , a transmembrane growth factor receptor , is frequently overexpressed in malignancies , causing activation of the phosphatidylinositol 3 kinase ( PI3K ) and extracellular signal regulated kinase ( ERK ) signal pathways . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| One of the major targets for the therapy in PCa can be epidermal growth factor receptor ( EGFR ) , which signals via the phosphoinositide 3 ' kinase ( PI3K ) / Akt and mitogen activated protein kinase ( MAPK ) pathways , among others . ^^^ Despite multiple reports of overexpression in PCa , the reliance on activated EGFR and its downstream signalling to the PI3K and / or MAPK / extracellular signal regulated kinase ( ERK ) pathways has not been fully elucidated . ^^^ PI3K inhibition , by LY 294002 or after PTEN transfection , restores EGFR stimulated Akt signalling and sensitizes the cells to pro apoptotic action of gefitinib . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Interestingly , EGFR PI3K interaction was also disrupted in these cells . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| The most advanced targeted agents currently under development interfere with function and expression of several signalling molecules , including the EGFR family ; the vascular endothelial growth factor and its receptors ; and cytoplasmic kinases such as Ras , PI3K and mTOR . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Agents targeting single pathways , including EGFR , IGF 1R , PI3K , and Ras , have been studied alone and in combination with radiation . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Our data demonstrate that EGFR induced signaling and Grb 2 are essential for formation of clathrin coated pits accommodating the EGFR , while activation of MAPK and PI3K is not required . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| This chronic switch in epithelial behavior exhibits genetic susceptibility and depends on persistent activation of EGFR signaling to PI3K that prevents apoptosis of ciliated cells and on IL 13 signaling that promotes transdifferentiation of ciliated to goblet cells . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Hyperoxia stimulates an Nrf 2 ARE transcriptional response via ROS EGFR PI3K Akt / ERK MAP kinase signaling in pulmonary epithelial cells . ^^^ Collectively , our data suggest that EGFR PI3K signaling through Akt and ERK kinases regulates ROS dependent , hyperoxia induced Nrf 2 activation in pulmonary epithelial cells . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Western blotting demonstrated that gefitinib blocked activation of the EGFR extracellular signal regulated kinase ( Erk ) pathway and the EGFR phosphoinositide 3 kinase ( PI3K ) Akt pathway after irradiation . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| EGFR activates PLC gamma 1 directly and activates Akt indirectly through phosphatidylinositol 3 kinase ( PI3K ) . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| The signaling pathway that is initiated by binding of epidermal growth factor receptor ( EGFR ) and results in sustained signaling through PI3K plays an important role in a tumor ' s response to ionizing radiation . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| We show here that EGF R transactivation was sensitive to pertussis toxin ( PTX ) and phosphoinositide 3 kinase ( PI3K ) inhibitors and that it occurred independently from Src activity , despite the observation of a strong impairment of LTD 4 induced DNA synthesis following Src inhibition . ^^^ CONCLUSION : Collectively , our data demonstrate that in HASMC LTD 4 stimulation of a Gi / o coupled CysLT 1 R triggers the transactivation of the EGF R through the intervention of PI3K and ROS . ^^^ While PI3K and ROS involvement is an early event , the activation of Src occurs downstream of EGF R activation and is followed by the classical Ras ERK1 / 2 signaling pathway to control G 1 progression and cell proliferation . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Pentagalloylglucose inhibits estrogen receptor alpha by lysosome dependent depletion and modulates ErbB / PI3K / Akt pathway in human breast cancer MCF 7 cells . ^^^ These findings suggested that 5GG might be a useful chemopreventive or therapeutic agent for hormone dependent breast cancer through suppressing the functions of ERalpha by lysosome dependent depletion and modulating the ErbB / PI3K / Akt pathway . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Using such a method , we show that whereas both ErbB 2 homodimers and ErbB 1 ErbB2 heterodimers were equally potent in activating the Ras / mitogen activated protein kinase pathway , the heterodimers were more potent in activating the phosphoinositide 3 ' kinase ( PI3K ) and phospholipase Cgamma 1 pathways than ErbB 2 homodimers . ^^^ The ability of heterodimers to induce invasion required the ErbB 1 kinase activity and required activation of PI3K , Ras / mitogen activated protein kinase , and phospholipase Cgamma 1 signaling pathways . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| EGF induced cell migration in a dose dependent manner ; EGF induced EGFR phosphorylation and downstream activation of c Jun N terminal protein kinase ( JNK ) , p 38 MAP kinase ( p 38 ) , extracellular signal regulated kinase ( ERK1 / 2 ) and AKT , were inhibited by PD 153035 ( EGFR inhibitor ) , JNKi ( JNK inhibitor ) , SB 203580 ( p 38 inhibitor ) , U 0126 ( MEK / ERK inhibitor ) , and LY 294002 ( PI3K / AKT inhibitor ) , respectively . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| EGFR and ErbB 4 had several docking sites for Grb 2 , while ErbB 3 was characterized by six binding sites for PI3K . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| The HSP 90 inhibitor 17 allylamino 17 demethoxygeldanamycin ( 17 AAG ) depletes some proteins involved in PI3K / AKT signaling , e . g . , ERBB 2 , epidermal growth factor receptor ( EGFR ) , and phosphorylated AKT ( p AKT ) . 17 AAG and paclitaxel were combined ( at a fixed 1 : 1 ratio of their IC ( 50 ) ) in four ovarian cancer cell lines that differ in expression of p AKT , EGFR , and ERBB 2 . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| ErbB RTK activation , mitogen activated protein kinase ( MAPK ) and phosphatidylinositol 3 kinase ( PI3K ) / p70S6K signaling , and clonogenic survival were determined for expression of each deletion mutant . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| AG 1478 , PD 98059 , and LY 294002 , inhibitors of EGF receptor ( EGFR ) tyrosine kinase , MAPK / extracellular signal regulated kinase ( ERK ) kinase , and phosphatidylinositol 3 kinase ( PI3K ) , respectively , inhibited the contraction and the activity of ERK1 / 2 that were elevated by EGF . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Phosphorylation of extracellular signal regulated kinase ( ERK ) , AKT ( a major substrate of phosphatidylinositol 3 ' kinase [ PI3K ] ) , Src at tyrosine Y 416 , and EGFR at Y 845 was analyzed by Western blotting with antibodies specific to phosphorylated proteins . ^^^ CONCLUSIONS : These results suggest that Src kinase mediates wound induced EGFR transactivation and participates in a pathway to activate the PI3K AKT pathway downstream of EGFR in HCECs . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| In isolated mouse carotid artery segments mounted in an arteriograph , ET 1 caused only a weak increase in isovolumetric tone in HB EGF deficient vessels , and this effect was mimicked by inhibition of EGFR tyrosine kinase or phosphoinositide 3 kinase ( PI3K ) in wild type arteries with or without endothelium , indicating a specific role in VSMCs . ^^^ EGFR or PI3K inhibitors had no effect on KCl induced contraction , which was normal in HB EGF deficient mice . ^^^ This effect was reproduced by preincubation of wild type VSMCs with EGFR inhibitor AG 1478 and PI3K inhibitors LY 294002 and wortmannin . ^^^ This functional cascade requires modulation of agonist induced calcium transient by EGFR and PI3K with extremely fast kinetics , suggesting a novel paradigm for GPCR mediated calcium signaling , which may offer future therapeutic targets . . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| Upon EGF treatment of MCF 7 or three colorectal carcinoma cell lines ( WiDr , DLD 1 , and LS174T ) , the EGF R coimmunoprecipitated with both p 85 alpha and Src . ^^^ These data demonstrate that EGF R is phosphorylated in vivo at non autophosphorylation sites and that these novel sites can act as docking sites for Src , P 85 alpha , and potentially other SH 2 containing proteins . ^^^ Src phosphorylation of the epidermal growth factor receptor at novel sites mediates receptor interaction with Src and P 85 alpha . ^^^ |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P27986 and P00533 |
Pubmed |
SVM Score :0.0 |
| NA |
|