| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.63401066 |
| CD 28 binds both PI3K and Grb 2 , whereas ICOS binds only PI3K . 0.63401066^^^ |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| Activation of the PI3K effector protein kinase B following ligation of CD 28 or Fas . ^^^ |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| The phosphatidylinositol 3 kinase ( PI3K ) and GRB 2 binding site in CD 28 is dispensable for optimal IL 2 production in Jurkat T cells . ^^^ The distal three tyrosines of CD 28 , however , are not required for recruitment of PI3K to CD 28 . ^^^ Furthermore , PI3K is recruited to CD 28 in JCaM 1 cells which lack LCK and in which EMT / ITK is not activated by ligation of CD 28 . ^^^ Thus optimal activation of LCK or EMT / ITK is not obligatory for recruitment of PI3K to CD 28 and thus is also not required for tyrosine phosphorylation of the YMNM motif in CD 28 . ^^^ |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| Engagement of CD 28 leads to its tyrosine phosphorylation and subsequent binding to Src homology 2 ( SH 2 ) containing proteins including the p 85 subunit of phosphatidylinositol 3 ' kinase ( PI3K ) ; however , the contribution of PI3K to CD 28 dependent costimulation remains controversial . ^^^ The inducible interaction of Grb 2 to the C terminal region of CD 28 may form the basis for PI3K independent signaling through CD28 . . ^^^ |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| Ligation of the TCR or CD 28 induces activation of phosphatidylinositol 3 kinase ( PI3K ) , the TEC family protein tyrosine kinase , EMT / ITK / TSK ( EMT ) , and the SRC family tyrosine kinase , LCK . ^^^ We report herein that inhibition of PI3K activity with the specific inhibitors LY 294002 and wortmannin markedly decreased EMT activation induced by CD 28 cross linking but not by CD 3 cross linking . ^^^ In contrast , PI3K inhibitors did not alter CD 28 or CD 3 cross linking or LCK induced EMT phosphorylation . ^^^ Consistent with the requirement of PI3K activity for CD 28 but not CD 3 induced stimulation of the EMT in vitro autokinase activity , a small but significant portion of cellular EMT associates with PI3K following CD 28 cross linking but not following CD 3 cross linking . ^^^ CD 28 induced association of EMT with PI3K also requires functional expression of LCK . ^^^ |
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| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| The complexities of CD 28 and CTLA 4 signalling : PI3K and beyond . ^^^ This review will focus on our current understanding of the biochemical signals that may be involved in regulating the different functional outcomes of CD 28 and CTLA 4 , with particular emphasis on the role played by the PI3K dependent signalling cascade . . ^^^ |
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| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| A particularly controversial matter is the role of phosphatidylinositol 3 kinase ( PI3K ) in CD 28 mediated costimulation . ^^^ It is known that the binding site for PI3K and Grb 2 lies nested within the YMNM motif of the CD 28 cytoplasmic domain . ^^^ To elucidate the role of PI3K during CD 28 mediated interleukin 2 ( IL 2 ) production , CD 28 YMNM point and deletion mutants were expressed in Jurkat cells . ^^^ Taken together , these data indicate that PI3K , when associated with the YMNM motif , may act as a negative mediator in CD 28 mediated IL 2 gene transcription . . ^^^ |
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| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| CD 28 costimulation mediates down regulation of p27kip1 and cell cycle progression by activation of the PI3K / PKB signaling pathway in primary human T cells . ^^^ Decreased abundance of cyclin dependent kinase inhibitor p 27 ( kip 1 ) , which requires simultaneous TCR / CD3 and CD 28 ligation , was dependent upon both MEK and PI3K activity . ^^^ Ligation of TCR / CD3 , but not CD 28 alone , resulted in activation of MEK targets extracellular signal related kinase 1 / 2 , whereas ligation of CD 28 alone was sufficient for activation of PI3K target protein kinase B ( PKB ; c Akt ) . ^^^ Thus , inactivation of the PI3K PKB target GSK 3 could substitute for CD 28 but not for CD 3 signals . ^^^ These results show that the PI3K PKB pathway links CD 28 to cell cycle progression and suggest that p 27 ( kip 1 ) integrates mitogenic MEK and PI3K dependent signals from TCR and CD 28 in primary T lymphocytes . . ^^^ |
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| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| T cell lines expressing CD8alpha / 28 chimeric receptors containing a mutation in tyrosine 173 to phenylalanine , which inhibits the recruitment of phosphatidylinositol 3 kinase ( PI3K ) to CD 28 , expressed higher levels of HIV 1 following T cell activation . ^^^ |
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| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| Here we show that CD 28 costimulation , acting through phosphatidylinositol 3 ' kinase ( PI3K ) and Akt , is required for T cells to increase their glycolytic rate in response to activation . ^^^ |
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| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| Here we demonstrate that CD 4 ( + ) T cells from CD 28 deficient mice show increased susceptibility to Fas mediated apoptosis via a phosphatidylinositol 3 kinase ( PI3K ) dependent pathway . ^^^ To understand how PI3K mediated signals downstream of CD 28 contribute to T cell survival , we examined Fas mediated apoptosis in T cells expressing an active form of PKBalpha . ^^^ These findings provide a novel link between CD 28 and an important apoptosis pathway in vivo , and demonstrate that PI3K / PKB signaling prevents apoptosis by inhibiting DISC assembly . . ^^^ |
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| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| ICOS costimulation led to greatly augmented levels of PI3K activity compared with CD 28 costimulation , whereas only CD 28 costimulation activated c jun N terminal kinase . ^^^ Our results show that even though the ICOS Src homology ( SH ) 2 binding domain strongly activated PI3K , it was unable to substitute for the CD 28 SH2 binding domain to induce high levels of IL 2 and Bcl 10 ( L ) . ^^^ |
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| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| Both CD 28 and its relative , inducible costimulator ( ICOS ) , have a binding motif for phosphatidylinositol 3 kinase ( PI3K ) in their cytoplasmic tail , and the binding of PI3K leads to activation of a serine / threonine kinase , Akt . ^^^ |
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| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| An inactivating mutation in the leucocyte specific PI3K isoform p110delta results in impaired TcR dependent proliferation under circumstances where CD 28 co stimulation is blocked or not required . ^^^ Recruitment and activation of PI3K by CD 28 promotes survival by inducing increased expression of Bcl 10 ( L ) . ^^^ However , CD 28 engages additional signals that regulate proliferation and interleukin 2 production independently of PI3K . ^^^ Thus a model emerges whereby PI3K is involved in both TcR and CD 28 signalling , but each receptor may only exploit a subset of the signalling pathways potentially controlled by PI3K activation . . ^^^ |
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| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| PI3K was identified early as a candidate for CD 28 signaling , but conflicting data during the past decade has left the role of PI3K unresolved . ^^^ We show that mutation of the PI3K interaction site in the cytosolic tail of CD 28 site disrupts the ability of CD 28 to recruit protein kinase C theta ; to the central supramolecular activation cluster ( c SMAC ) region of the immunological synapse , promote NF kappaB nuclear translocation , and enhance IL 2 gene transcription . ^^^ In contrast , mutation of the PI3K interaction site had no effect on the ability of CD 28 to enhance IL 2 mRNA stability . ^^^ These results suggest that two distinct pathways mediate CD 28 induced up regulation of IL 2 expression , a PI3K dependent pathway that may function through the immunological synapse to enhance IL 2 transcription and a PI3K independent pathway that induces IL 2 mRNA stability . . ^^^ |
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| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| We show that although signaling through the TCR is sufficient to stimulate transcription of Bcl 10 ( L ) mRNA , CD 28 , by activating PI3K and mammalian target of rapamycin , provides a critical signal that regulates the translation of Bcl 10 ( L ) transcripts . ^^^ These results demonstrate that CD 28 relieves the translational inhibition of Bcl 10 ( L ) in a PI3K / mammalian target of rapamycin dependent manner . . ^^^ |
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| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| Importantly , a PKC Ras MEK / PI3K cascade links costimulation of PB T through TCR / CD3 and CD 28 to activation of cofilin through dephosphorylation . ^^^ |
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| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| In this study , we show that ligation of CD 28 by its natural ligand B 7 1 / CD80 , induces tyrosine phosphorylation of Gab 2 and its coassociation with Src homology phosphatase ( SHP ) 2 and class IA PI3K in Jurkat cells . ^^^ Together , these data demonstrate that CD 28 stimulation of T cells is sufficient to induce an inhibitory multimeric signaling complex involving Gab 2 , SHP 2 , and PI3K . ^^^ |
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| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| Together , our findings indicate that the TCR , CD 28 , and IL 2 independently control T cell proliferation via distinct signaling pathways involving PI3K and mTOR . ^^^ |
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| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| CD 28 signaling through PI3K results in the recruitment of protein kinase C ( PKC ) theta to the cSMAC , activation of NF kappaB , and induction of IL 2 transcription . ^^^ |
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| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| We found that TCR stimulation alone , without CD 28 costimulation , is sufficient to induce hyperactivation of the PI3K pathway , which leads to enhanced IL 2 production by naive PTENDeltaT T cells . ^^^ |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P10747 and P27986 |
Pubmed |
SVM Score :0.0 |
| NA |
|