| Interacting proteins: P25942 and P27986 |
Pubmed |
SVM Score :0.0 |
| CD 40 ligation induces macrophage IL 10 and TNF alpha production : differential use of the PI3K and p42 / 44 MAPK pathways . ^^^ These observations suggest that CD 40 ligation induces macrophage IL 10 and TNF alpha production , the mechanism of which is p70S6K dependent yet bifurcates at the level of PI3K and p42 / 44 MAPK . . ^^^ |
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| Interacting proteins: P25942 and P27986 |
Pubmed |
SVM Score :0.0 |
| We show that cross linking CD 40 , using either soluble CD40L ( sCD40L ) or anti CD 40 monoclonal antibody ( mAb ) , induces phosphatidylinositol 3 kinase ( PI3K ) activity and activates its downstream effector AKT in MM . 1S cells . ^^^ Using pharmacologic inhibitors of PI3K and MEK , as well as adenoviruses expressing dominant negative and constitutively expressed AKT , we demonstrate that PI3K and AKT activities are required for CD 40 induced MM cell migration . ^^^ We further demonstrate that CD 40 induces nuclear factor ( NF ) kappa B activation as a downstream target of PI3K / AKT signaling , and that inhibition of NF kappa B signaling using specific inhibitors PS 1145 and SN 50 completely abrogates CD 40 induced MM migration . ^^^ Finally , we demonstrate that urokinase plasminogen activator ( uPA ) , an NF kappa B target gene , is induced by CD 40 ; and conversely , that uPA induction via CD 40 is blocked by PI3K and NF kappa B inhibitors . ^^^ Our data therefore indicate that CD 40 induced MM cell migration is primarily mediated via activation of PI3K / AKT / NF kappa B signaling , and further suggest that novel therapies targeting this pathway may inhibit MM cell migration associated with progressive MM . . ^^^ |
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| Interacting proteins: P25942 and P27986 |
Pubmed |
SVM Score :0.0 |
| The enhanced Akt activity induced by stimulation of endothelial CD 40 was temporarily correlated with the association of CD 40 with TRAF 6 , c Cbl , and the p 85 subunit of PI3K . ^^^ Expression of negative dominant Akt inhibited the activation of endogenous Akt through CD 40 stimulation , despite the observation that association of CD 40 with TRAF 6 , c Cbl , and PI3K was intact . ^^^ In conclusion , these results suggest that endothelial CD 40 , through activation of the PI3K / Akt signaling pathway , regulates cell survival , proliferation , migration , and vessel like structure formation , all steps considered critical for angiogenesis . . ^^^ |
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| Interacting proteins: P25942 and P27986 |
Pubmed |
SVM Score :0.0 |
| We have found that inhibition of CD 40 signaling on the phosphatidylinositol 3 kinase ( PI3K ) and ERK MAPK but not on the p 38 MAPK axis disrupts this balance and sensitizes carcinoma cells to CD 40 mediated cell death . ^^^ The CD 40 mediated PI3K and ERK activities were found to converge on the regulation of protein synthesis in carcinoma cells via a pathway involving the activation of p 90 ribosomal S 6 kinase ( p90Rsk ) and p70S6 kinases , upstream of the translation elongation factor eEF 2 . ^^^ In addition , CD 40 ligation was found to mediate a PI3K and mammalian target of rapamycin ( mTOR ) dependent phosphorylation of 4E BP 1 and its subsequent dissociation from the mRNA cap binding protein eIF4E as well as an ERK dependent phosphorylation of eIF4E , thus promoting translation initiation . ^^^ Concomitantly , the antiapoptotic protein cFLIP was found to be induced in CD 40 ligand stimulated carcinoma cells in a PI3K , ERK , and mammalian target of rapamycin ( mTOR ) dependent manner and down regulation of cFLIPS expression sensitized to CD 40 mediated carcinoma cell death . ^^^ These data underline the significance of the PI3K and ERK pathways in controlling the balance between CD 40 mediated survival and death signals through the regulation of the protein synthesis machinery . ^^^ |
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| Interacting proteins: P25942 and P27986 |
Pubmed |
SVM Score :0.0 |
| Immunoprecipitation studies revealed that ligation of CD 40 on EC promoted an increased association of Ras with its effector molecules Raf , Rho , and phosphatidylinositol 3 kinase ( PI3K ) . ^^^ Also , wortmanin and a dominant inhibitory mutant of PI3K inhibited CD 40 induced overexpression of VEGF . ^^^ Together these findings demonstrate that both Ras and PI3K are intermediaries in CD 40 induced regulation of VEGF in EC . ^^^ |
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| Interacting proteins: P25942 and P27986 |
Pubmed |
SVM Score :0.0 |
| PI3K signaling is promoted by stimulatory receptors such as surface immunoglobulin , CD 40 , Toll like receptors and cytokine receptors , and opposed by the inhibitory receptor FcgammaRIIB 1 . ^^^ |
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| Interacting proteins: P25942 and P27986 |
Pubmed |
SVM Score :0.0 |
| B cell receptor ( BCR ) cross talk : CD 40 engagement creates an alternate pathway for BCR signaling that activates 1 kappa B kinase / I kappa B alpha / NF kappa B without the need for PI3K and phospholipase C gamma . ^^^ |
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| Interacting proteins: P25942 and P27986 |
Pubmed |
SVM Score :0.0 |
| Stimulation of mesangial CD 40 with sCD 154 rescued HMC from oxLDL dependent apoptosis , while two unrelated pharmacological inhibitors of PI3K LY 294002 and wortmannin abrogated this anti apoptotic effect , suggesting an involvement of the PI3K / Akt pathway . ^^^ Indeed , CD 154 induced a rapid enhancement in Akt enzymatic activity , that was temporarily correlated with the association of CD 40 with TRAF 3 , TRAF 6 , c Cbl and the p 85 subunit of PI3K . ^^^ In conclusion , these results suggest that CD 40 stimulation protects HMC from toxic effects of oxLDL by promoting PI3K / Akt dependent cell survival . . ^^^ |
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| Interacting proteins: P25942 and P27986 |
Pubmed |
SVM Score :0.0 |
| Rapid CD 40 mediated rescue from CD 95 induced apoptosis requires TNFR associated factor 6 and PI3K . ^^^ |
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| Interacting proteins: P25942 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P25942 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P25942 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P25942 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P25942 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P25942 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P25942 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P25942 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P25942 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P25942 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
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