Pubmed abstracts for Protein-Protein Interaction search result :


Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.80731335
Expressed in a murine myeloma , TRAP was identified as a ligand for CD 40 by binding to a soluble CD 40 construct . 0.80731335^^^ Cloning of TRAP , a ligand for CD 40 on human T cells . 0.51966786^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.83748955
Interaction of TRAP with CD 40 on B cells is of paramount importance for immunoglobulin class switching and subsequent synthesis of IgG , IgA or IgE in vivo . 0.83748955^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.61706967
The interaction of TRAP / CD40L with CD 40 thus provides a very critical link between the cellular and the humoral part of the immune system . 0.61706967^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.87447655
The resultant failure of TRAP to interact with CD 40 on functionally intact B cells is responsible for the observed immunoglobulin isotype defect in HIGM1 . . 0.87447655^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.93226749
The coding region of TNF receptor associated factor 2 ( TRAF 2 ) , which is known to interact with CD 40 for NF kappaB induction , was also found to be normal in B cell lines deficient in NF kappaB induction . 0.93226749^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.52705127
The spacing between the CD 40 binding sites on TRAF 2 supports an elegant signaling mechanism in which trimeric , extracellular ligands preorganize the receptors to simultaneously recognize three sites on the TRAF trimer . . 0.52705127^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.50036617
In this study , using isothermal titration calorimetry ( ITC ) , we report thermodynamic characterization of the interaction between TRAF 2 and monomeric peptide sequences from TNFR members , including TNFR 2 , CD 40 , CD 30 , Ox 40 , and 4 1BB , and the Epstein Barr virus ( EBV ) transforming protein , latent infection membrane protein 1 ( LMP 1 ) . 0.50036617^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.74420761
Interestingly , the role of PKD was dependent upon the association of CD 40 with TRAF 2 , and was inhibited by the binding of TRAF 3 , revealing a novel functional link between these two classes of signaling molecules . . 0.74420761^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Interactions between gp 39 ( CD40L , TRAP , T BAM ) on activated T cells and CD 40 on antigen presenting cells play an important role in regulating antibody production by B cells , cytokine production by monocytes , and other immune responses which require T cell `` help ' ' . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
A region of CRAF 1 was similar to the TNF alpha receptor associated factors TRAF 1 and TRAF 2 and so defined a shared TRAF C domain that was necessary and sufficient for CD 40 binding and homodimerization . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
The interaction between gp 39 ( CD40L , TRAP , T BAM ) on activated T cells and mast cells and CD 40 on antigen presenting cells modulates immune responses . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
TRAF 2 mediated activation of NF kappa B by TNF receptor 2 and CD 40 . ^^^ A truncated derivative of TRAF 2 lacking an amino terminal RING finger domain was a dominant negative inhibitor of NF kappa B activation mediated by TNF R 2 and CD 40 . ^^^ Thus , TRAF 2 is a common mediator of TNF R 2 and CD 40 signaling . . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Spontaneous apoptosis of dendritic cells is efficiently inhibited by TRAP ( CD 40 ligand ) and TNF alpha , but strongly enhanced by interleukin 10 . ^^^ TNF related activation protein ( TRAP ; CD 40 ligand ) and interleukin 10 ( IL 10 ) on induction or prevention of apoptotic cell death in these cells . ^^^ Furthermore , IL 10 led to the down regulation of various surface antigens , especially of CD 86 and CD 54 , whereas TNF alpha and TRAP enhanced the expression of MHC class 1 and 2 antigens and of the accessory molecules CD 40 , CD 54 , CD 80 and CD 86 . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
We show that fixed cells and the cell membranes from a T cell line , BMS 2 , that expresses high levels of the CD 40 ligand gp 39 ( also called TRAP , TBAM , or CD40L ) stimulate both the expression of mRNA and the production of MMPs by human monocytic cells . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
TRAF 2 action is required for activation of the transcription factor NF kappaB triggered by TNF and the CD 40 ligand . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
TRAF 2 is required for CD 40 and TNF mediated activation of the transcription factor NF kappa B . ^^^ Overexpression of 1 TRAF inhibits TRAF 2 mediated NF kappa B activation signaled by CD 40 and both TNF receptors . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
In vitro binding assays revealed that TRAF 5 associates with the cytoplasmic tail of CD 40 , but not with the cytoplasmic tail of tumor receptor factor receptor type 2 , which associates with TRAF 2 . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
The TNF R 2 associated factor TRAF 2 has been shown to mediate activation of NF kappa B by TNF R 2 and CD 40 . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Deletion analysis showed that residues 246 269 of CD 40 which are required for its association with TRAF 2 , TRAF 3 , and TRAF 5 are dispensable for its interaction with TRAF 6 , whereas residues 230 245 were required . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Induction , regulation , and function of soluble TRAP ( CD 40 ligand ) during interaction of primary CD4+ CD45RA+ T cells with dendritic cells . ^^^ To assess the induction , regulation , and the relative roles of cell surface tumor necrosis factor related activation protein ( TRAP ; CD 40 ligand ) and the soluble form of TRAP ( sTRAP ) in the initial phase of T cell activation , primary CD4+ CD45RA+ ( naive ) T cells were co cultured with mature Langerhans ' cells ( mLC ) in the presence of superantigen . ^^^ After appearing on the cell surface , TRAP was rapidly down regulated by a mechanism triggered through interaction of TRAP with CD 40 on mLC . ^^^ In terms of function , sTRAP can not compete with cell surface TRAP for ligation of CD 40 on mLC , indicating that sTRAP release is not a mechanism for termination of the TRAP / CD40 interaction . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Clones corresponding to genes coding for TRAF 1 , TRAF 2 , and TRAF 3 molecules , postulated to be involved in signalling via the TNF and CD 40 receptors , were isolated . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
A 20 , an anti apoptotic protein which interacts with TRAF 2 and blocks CD 40 mediated NF kappaB activity , also blocked NF kappaB and IL 6 secretion in LMP 1 transfected epithelial cells . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Studies with human B cells show that the binding of CD 154 ( gp 39 , CD40L ) to CD 40 recruits TNF receptor associated factor 2 ( TRAF 2 ) and TRAF 3 to the receptor complex , induces the downregulation of the nonreceptor associated TRAFs in the cell and induces an increased expression of Fas on the cell surface . ^^^ Combined signaling through the interluekin 4 receptor and CD 40 induces an increased expression of Fas with a commensurate increase in the level of TRAF 2 , but not TRAF 3 , that is recruited to the receptor complex . ^^^ In contrast , engagement of the membrane immunoglobulin and CD 40 limits Fas upregulation and reduces the recruitment of TRAF 2 , relative to TRAF 3 , to the CD 40 receptor complex . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
A threonine residue at position 234 , previously shown to be important for CD 40 association with TNF receptor associated factor 2 ( TRAF 2 ) , TRAF 3 , and TRAF 5 , was not required for NF kappa B activation . ^^^ This suggests that in B cells , CD 40 induced NF kappa B activation can occur independently of TRAF 2 and TRAF 5 association . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
CD 40 mediated signals inhibit the binding of TNF receptor associated factor 2 to the CD 40 cytoplasmic domain . ^^^ TNF receptor associated factor 2 ( TRAF 2 ) is a signal transducing protein associated with the CD 40 cytoplasmic domain . ^^^ TNF receptor associated factor 2 ( TRAF 2 ) is a signal transducing protein associated with the CD 40 cytoplasmic domain . ^^^ It has been hypothesized that during signal transduction , TRAF 2 must be released from CD 40 in order for it to interact with downstream signaling molecules . ^^^ We found that CD 40 and TRAF 2 were constitutively associated with each other in a human B cell line . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
TRAF 1 , TRAF 2 , TRAF 3 , and TRAF 6 , but not TRAF 4 or TRAF 5 , bound directly to the CD 40 cytoplasmic domain . ^^^ CD 40 interactions with TRAF 2 and TRAF 3 were stronger than the interactions with TRAF 1 and TRAF 6 . ^^^ Using peptides with progressive deletions , a minimal TRAF 1 , TRAF 2 , and TRAF 3 binding region was mapped to the PVQET sequence in the CD 40 cytoplasmic domain . ^^^ These studies demonstrate that the CD 40 cytoplasmic domain contains two nonoverlapping TRAF binding regions and suggest that TRAF 1 , TRAF 2 , and TRAF 3 could bind competitively to one site . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
This amino acid alignment contains the EEEG sequence , which is essential for interaction of CD 30 or CD 40 with TRAFs ( TRAF 1 and TRAF 2 , but not TRAF 3 ) , and also contains the PIQED sequence , which is similar to PXQXT that is known to be necessary for interaction of TNF receptor 2 and CD 30 with TRAFs ( TRAF 1 , 2 , and 3 ) . . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Although four members of the tumor necrosis factor receptor associated factor ( TRAF ) family , including TRAF 2 , TRAF 3 , TRAF 5 , and TRAF 6 , bind to the CD 40 cyt , how each TRAF protein contributes to the NFkappaB activation by CD 40 is not clear . ^^^ Here we report that TRAF 2 , TRAF 3 , and TRAF 5 bind cyt C , whereas TRAF 6 binds cyt N . cyt N is conserved poorly between human and mouse CD 40 , while cyt C is highly conserved . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Specificities of CD 40 signaling : involvement of TRAF 2 in CD 40 induced NF kappaB activation and intercellular adhesion molecule 1 up regulation . ^^^ Several tumor necrosis factor receptor associated factor ( TRAF ) family proteins including TRAF 2 , TRAF 3 , TRAF 5 , and TRAF 6 , as well as Jak 3 , have been implicated as potential mediators of CD 40 signaling . ^^^ An extensive in vitro binding study indicated that TRAF 2 and TRAF 3 bind to the CD 40 cytoplasmic tail ( CD40ct ) with much higher affinity than TRAF 5 and TRAF 6 and that TRAF 2 and TRAF 3 bind to different residues of the CD40ct . ^^^ Using CD 40 mutants incapable of binding TRAF 2 , TRAF 3 , or Jak 3 , we found that the TRAF 2 binding site of the CD40ct is critical for NF kappaB and stress activated protein kinase activation , as well as the up regulation of the intercellular adhesion molecule 1 ( ICAM 1 ) gene , whereas binding of TRAF 3 and Jak 3 is dispensable for all of these functions . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Phosphorylation of TRAF 2 inhibits binding to the CD 40 cytoplasmic domain . ^^^ TRAF 2 is a signal transducing adaptor molecule which binds to the CD 40 cytoplasmic domain . ^^^ Furthermore , the phosphorylation status of TRAF 2 had significant effects on the ability of the protein to bind to CD 40 , as evidenced by our observations that the CD 40 cytoplasmic domain interacted preferentially with underphosphorylated TRAF 2 and that phosphatase treatment significantly enhanced the binding of TRAF 2 to CD 40 . ^^^ We conclude from these studies that the phosphorylation of TRAF 2 is likely to play an important role in regulating signaling by virtue of its ability to influence the CD 40 TRAF2 interaction . . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
This is the same region of CD 40 required for binding the TNF receptor associated factor 2 ( TRAF 2 ) , TRAF 3 , and TRAF 5 adapter proteins . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
The core binding site for TRAF 1 , TRAF 2 , and TRAF 3 in CD 40 could be minimally substituted . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Cutting edge : contrasting roles of TNF receptor associated factor 2 ( TRAF 2 ) and TRAF 3 in CD 40 activated B lymphocyte differentiation . ^^^ We examined the contributions of TNF receptor associated factor 2 ( TRAF 2 ) and TRAF 3 to CD 40 activated differentiation in mouse B cells transfected with inducible TRAF and dominant negative TRAF cDNAs . ^^^ We find that binding of TRAF 2 and TRAF 3 to CD 40 is not required for the induction of Ab secretion , but that both TRAF molecules can regulate the activation process . ^^^ In contrast , TRAF 2 appears to play a positive role in B cell differentiation , and this activity is apparent even when its binding site on CD 40 is disrupted . . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
In contrast to TRAF 2 and TRAF 3 , direct binding of TRAF 1 , TRAF 4 , TRAF 5 , or TRAF 6 to CD 40 was not detected . ^^^ CD 40 mutants with impaired binding to TRAF 2 , TRAF 3 , or both of these proteins completely retained the ability to activate NF kappaB and Jun N terminal kinase ( JNK ) , implying that CD 40 can stimulate TRAF 2 and TRAF 3 independent pathways for NF kappaB and JNK activation . ^^^ A carboxyl truncation mutant of CD 40 lacking the last 32 amino acids required for TRAF 2 and TRAF 3 binding , CD 40 ( Delta 32 ) , mediated NF kappaB induction through a mechanism that was suppressible by co expression of TRAF 6 ( DeltaN ) , a dominant negative version of TRAF 6 , but not by TRAF 2 ( DeltaN ) , implying that while TRAF 6 does not directly bind CD 40 , it can participate in CD 40 signaling . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Here we have defined the oligomeric structure of recombinant TRAF domains that directly interact with CD 40 and quantitated the affinities of TRAF 2 and TRAF 3 for CD 40 . ^^^ In surface plasmon resonance studies , a hierarchy of affinity of trimeric TRAFs for trimeric CD 40 was found to be TRAF 2 > TRAF 3 > > TRAF 1 and TRAF 6 . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
The intracellular tail of IL 15Ralpha shows sequence homologies to the TRAF 2 binding motifs of CD 30 and CD 40 . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
TRAF 2 deficiency results in hyperactivity of certain TNFR 1 signals and impairment of CD 40 mediated responses . ^^^ Using these double knockout mice , we show that in the absence of TRAF 2 , the T helper dependent antibody response , CD 40 mediated proliferation , and NF kappaB activation are defective . ^^^ These data demonstrate two important roles of TRAF 2 , one as a negative regulator of certain TNFR 1 signals and the other as a positive mediator of CD 40 signaling . . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Crystal structures of the TRAF domain of human TRAF 2 in complex with peptides from the TNFR family members CD 40 , CD 30 , Ox 40 , 4 1BB , and the EBV oncoprotein LMP 1 revealed a conserved binding mode . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
In particular , Bcl 2 , TNF receptor associated factor 2 ( TRAF 2 ) , and TRAF 4 were clearly inducible via CD 40 in B cells but not in DCs . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
In addition , CD 40 mutants previously shown to lack binding to TRAF 2 and 3 are fully capable of inducing IL 6 production . ^^^ Thus , CD 40 mediated IL 6 induction is independent of NF kappaB activation and the binding of TRAF 2 and 3 , but CD 40 must be engaged by trimeric CD 154 on cell membranes to activate production of IL 6 . . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Using CD 40 mutants with impairments in their ability to bind selected TNF receptor associated factor ( TRAF ) family proteins , we observed that CD 40 mediated transcriptional induction of the germ line Ig Cgamma 1 and Ig Cepsilon promoters was markedly reduced by mutations that prevent TRAF 2 , TRAF 3 , TRAF 5 or TRAF 6 binding . ^^^ Moreover , co expression of trans dominant inhibitory forms of TRAF 2 , 3 , 5 or 6 with wild type CD 40 also suppressed induction of these promoters . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
We show for the first time that engagement of CD 40 in intact B cells induces the rapid translocation of TRAF 2 from the cytoplasm to the plasma membrane . ^^^ We found that CD 40 engagement also results in its recruitment , together with TRAF 2 and TRAF 3 , to membrane microdomains , regions of the plasma membrane enriched in signaling molecules such as the Src family kinases . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
In transfected cells , TTRAP inhibits in a dose dependent manner the transcriptional activation of a nuclear factor kappaB ( NF kappaB ) dependent reporter mediated by CD 40 , TNF R 75 or Phorbol 12 myristate 13 acetate ( PMA ) and to a lesser extent by TRAF 2 , TRAF 6 , TNF alpha , or interleukin 1beta ( IL 1beta ) . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
CD 40 engagement also leads to a membrane raft restricted recruitment of tumor necrosis factor ( TNF ) receptor associated factor ( TRAF ) 3 and , to a lesser extent , TRAF 2 , to CD 40 ' s cytoplasmic tail . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
TRAF 2 suggests that CD 40 may assume different conformations when bound to different TRAF family members . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
TRAF 1 was also highly inducible by CD 40 ligand in cultured germinal center B cells , whereas TRAF 2 , TRAF 3 , TRAF 5 , and TRAF 6 were relatively unchanged . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Both signals were partially dependent upon induction of TNF alpha and IL 6 , and the cytoplasmic adaptor molecule TNF receptor associated factor 2 is involved in both R 848 and CD 40 mediated differentiation . . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Transiently expressed soluble trimeric CD 40 cytoplasmic domain was isolated as complexes that contained TRAF 2 , TRAF 3 , TRAF 5 , TRAF 6 , and the inhibitor of apoptosis protein ( c IAP 1 ) . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
The data presented here show that the shared binding site for TRAF 2 and TRAF 3 accounts for receptor internalization , and the majority of signaling through CD 40 , but is redundant with the TRAF 6 binding site for activation of p 38 and NFkappaB signaling pathways . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Role of TNF receptor associated factor 2 in the activation of IgM secretion by CD 40 and CD120b . ^^^ Previously , we found that a dominant negative TRAF 2 molecule inhibits CD 40 mediated Ab secretion by the mouse B cell line CH12 . ^^^ However , disruption of the TRAF 2 binding site in the cytoplasmic domain of CD 40 does not diminish the ability of CD 40 to stimulate Ab secretion , nor is this mutation able to circumvent the inhibition of Ab secretion by dominant negative TRAF 2 . ^^^ Furthermore , although both CD 40 and CD120b can bind TRAF 2 , TRAF 2 dependent CD 40 signals can not substitute for TRAF 2 dependent CD120b signals in the activation of IgM secretion . ^^^ Our results indicate a potentially important role for CD120b in the activation of IgM secretion and that TRAF 2 is used by CD 40 and CD120b in distinct ways . . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Signaling via the TNF R family member CD 40 has recently been shown to result in recruitment of TRAF 2 to plasma membrane detergent resistant microdomains ( lipid rafts ) as well as to subsequently initiate TRAF 2 degradation . ^^^ We show here that CD 40 mediated TRAF 2 degradation requires the zinc binding RING domain of TRAF 2 and is preceded by TRAF 2 ubiquitination , suggesting that the TRAF 2 RING may promote ubiquitination although the RING itself is not a target of ubiquitination . ^^^ Several approaches show that ubiquitination and proteasomal activity are integral to TRAF 2 degradation , and inhibition of this process potentiates CD 40 signaling . . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Stable transfectants expressing wild type or mutant forms of the cytoplasmic domain of CD 40 suggested that TRAF 3 , but not TRAF 2 , binding was essential for CD 40 mediated RANTES expression . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Cutting edge : molecular mechanisms of synergy between CD 40 and the B cell antigen receptor : role for TNF receptor associated factor 2 in receptor interaction . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Among the six known TRAF proteins , TRAF 2 , 3 , 5 , and 6 associated with CD 40 in an unstimulated state , and the levels of these four proteins were unaffected by anti CD 40 stimulation . ^^^ Antisense oligodeoxynucleotide ( ODN ) for TRAF 3 inhibited CD 40 induced activation of MEK 1 ERK pathway by decreasing expression of TRAF 3 protein , but antisense ODNs for TRAF 2 , 5 , and 6 were ineffective . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
The binding site for TRAF 2 and TRAF 3 but not for TRAF 6 is essential for CD 40 mediated immunoglobulin class switching . ^^^ To define the role of TRAF proteins in CD 40 dependent isotype switching in B cells , we introduced wild type ( WT ) and mutant CD 40 transgenes that lacked the binding motifs for TRAF 6 ( CD40deltaTRAF6 ) , TRAF 2 and TRAF 3 ( CD40deltaTRAF2 / 3 ) , or both ( CD40deltaTRAFs ) into B cells of CD 40 ( / ) mice . ^^^ These results suggest that binding to TRAF 2 and / or TRAF 3 but not TRAF 6 is essential for CD 40 isotype switching and activation in B cells . . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Upon receptor engagement , TRAF 2 is recruited to CD 40 and translocates to lipid rafts in a RING finger dependent process , which enables the activation of downstream signaling cascades including c Jun NH ( 2 ) terminal kinase ( JNK ) and nuclear factor ( NF ) kappaB . ^^^ Although TRAF 1 can displace TRAF 2 and CD 40 from raft fractions , it promotes the ability of TRAF 2 activate signaling over a sustained period of time . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
The critical role of TRAF 1 in the regulation of TRAF 2 dependent JNK signaling is particular to the TRAF binding domain of LMP 1 , since a homologous region in the cytoplasmic tail of CD 40 or the TRADD interacting domain of LMP 1 signal on the JNK axis independently of TRAF 1 status . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Mutation of the distinct binding sites for TNF receptor associated factor 6 ( TRAF 6 ) and for TRAF 2 , 3 , and 5 in the CD 40 cytoplasmic domain revealed their independent contributions to DC maturation and activation of NF kappaB . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
The fusion of the transmembrane domain of LMP 1 to signaling domains of CD 40 , TNF R 1 and Fas activates their signaling ; we demonstrate that a fusion of LMP 1 with CD 40 recruits TRAF 2 intracellularly . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Tumor necrosis factor receptor associated factor 2 ( TRAF 2 ) deficient B lymphocytes reveal novel roles for TRAF 2 in CD 40 signaling . ^^^ We demonstrate that TRAF 2 participates in synergy between CD 40 and B cell antigen receptor signals , and in CD 40 mediated , TNF dependent IgM production . ^^^ We also find that TRAF 2 participates in the degradation of TRAF 3 associated with CD 40 signaling , a role that may limit inhibitory actions of TRAF 3 . ^^^ Finally , we show that TRAF 2 and TRAF 6 have overlapping functions in CD 40 mediated NF kappaB activation and CD 80 up regulation . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
CD 40 signaling through a newly identified tumor necrosis factor receptor associated factor 2 ( TRAF 2 ) binding site . ^^^ In this report , we identify a second TRAF 2 binding site in the CD 40 C terminus . ^^^ The binding motif `` SVQE ' ' fits into the major TRAF 2 binding consensus sequence , and its disruption resulted in the loss of remaining CD 40 functions . ^^^ Hence , like CD 30 , the CD 40 cytoplasmic tail contains two distinct and functionally important TRAF 2 binding sites . . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Tumor necrosis factor receptor associated factor ( TRAF ) 1 regulates CD 40 induced TRAF 2 mediated NF kappaB activation . ^^^ The majority of cytoplasmic TRAF 2 GFP and , to a lesser extent , TRAF 3 GFP , but not TRAF 1 GFP or TRAF 4 GFP , translocated into CD 40 signaling complexes within a few minutes after CD 40 triggering with the CD 40 ligand . ^^^ The inhibitor of apoptosis proteins cIAP 1 and cIAP 2 were also recruited by TRAF 2 to sites of CD 40 signaling . ^^^ An excess of TRAF 2 allowed recruitment of TRAF 1 GFP to sites of CD 40 signaling , whereas an excess of TRAF 1 abrogated the interaction of TRAF 2 and CD 40 . ^^^ Because of the trimeric organization of TRAF proteins , we propose that the stoichiometry of TRAF 1 TRAF2 heteromeric complexes ( ( TRAF 2 ) 2 TRAF 1 versus TRAF 2 ( TRAF 1 ) 2 ) determines their capability to mediate CD 40 signaling but has no major effect on TNF signaling . . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Results show that phosphorylation of TRAF 2 is increased upon BCR but not CD 40 engagement and that of the potentially phosphorylated residues of TRAF 2 , tyrosine 484 is crucial for BCR CD 40 synergy . ^^^ These findings suggest a model in which Btk contributes to the enhancement of the CD 40 response by TRAF 2 in a PKD dependent manner . . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
From the present results it is possible that reduction of N glycosylation of the heavy chain of IgM by SW treatment may reduce anti IgM induced growth inhibition , and reduction in anti IgM induced growth inhibition due to altered N glycosylation may enhance CD 40 CD40L mediated cell survival through TRAF 2 which interacts with both IgM and CD 40 in HBL 2 cells . . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Since TRAF 2 and TRAF 6 play important roles in CD 40 signaling and TRAF 6 plays an important role in TLR 4 signaling , we examined the role of RIP in signaling via CD 40 and TLR 4 . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
We used a murine syngeneic bone marrow transplant ( BMT ) model , in which administration of anti CD 40 antibody early after BMT results in overproduction of interleukin 12 ( IL 12 ) and interferon gamma ( IFN gamma ) , and lethal gut toxicity to examine the protective effect of the spin trap inhibitor , alpha phenyl tert butyl nitrone ( PBN ) . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Ligation of CD 40 on Ramos B cells by recombinant CD 154 caused TRAF 2 and TRAF 3 to dissociate , whereas overexpression of TRAF 3 in Ramos B cells inhibited CD 154 induced TRAF 2 mediated activation of NF kappaB . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
The CD 40 receptor and the Epstein Barr virus oncoprotein LMP 1 are both members of the TNF receptor family and share several signaling mediators , including TRAF 2 and TRAF 3 . ^^^ Previous publications have suggested that both TRAF 2 and TRAF 3 move into lipid rafts upon LMP 1 expression or CD 40 activation , whereas their proteolysis is only enhanced by CD 40 . ^^^ However CD 40 induced proteolysis of TRAF 2 has only been reported in murine cells , and there are conflicting data regarding translocation of TRAF 2 into lipid rafts . ^^^ We therefore investigated TRAF 2 and TRAF 3 modifications induced by CD 40 and LMP 1 signaling in a panel of human cell lines of lymphoid and epithelial origins . ^^^ Upon CD 40 stimulation , a marked redistribution of TRAF 2 into the buoyant raft fraction was observed in all cell lines and was often associated with a similar redistribution of TRAF 3 . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Both CD 40 and CD120b bind TNF receptor associated factor 2 ( TRAF 2 ) upon ligand stimulation . ^^^ Role of tumor necrosis factor ( TNF ) receptor associated factor 2 ( TRAF 2 ) in distinct and overlapping CD 40 and TNF receptor 2 / CD120b mediated B lymphocyte activation . ^^^ Wild type and TRAF 2 deficient B cells expressing CD 40 or the hybrid molecule ( human ) CD 40 ( mouse ) CD120b were examined . ^^^ CD 40 and CD120b mediated IgM secretion were partly TRAF 2 dependent , but only CD 40 required TRAF 2 for c Jun N terminal kinase activation . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
These TRAF 2 deficient B cells could not proliferate or activate the canonical NF kappaB pathway in response to CD 40 ligation . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
In this study , we found that receptor induced TRAF degradation limits TRAF 2 dependent CD 40 signals to murine B cells . ^^^ Chimeras containing the TRAF 2 zinc ( Zn ) domains induced effective degradation , if attached to a TRAF domain that binds to the PXQXT motif of CD 40 . ^^^ Our data indicate that TRAF 2 serves as the master regulator of TRAF degradation in response to CD 40 signaling , and this function is dependent upon both the TRAF Zn domains and receptor binding position . . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Overexpression of USP 31 in HEK 293T cells inhibited TNFalpha , CD 40 , LMP 1 , TRAF 2 , TRAF 6 and IKKbeta mediated NF kappaB activation , but did not inhibit Smad mediated transcription activation . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Platelet aggregation , dense granule secretion , alpha granule secretion ( PAI 1 and soluble CD 40 ligand levels ) and procoagulant responses ( annexin 5 and microparticle formation ) were assessed using collagen and thrombin receptor activating peptide ( TRAP ) as agonists . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
TRAF 6 is required for TRAF 2 dependent CD 40 signal transduction in nonhemopoietic cells . ^^^ In this study we present evidence that the CD 40 interacting proteins TRAF 2 and TRAF 6 play an important physiological role in CD 40 signaling in nonhemopoietic cells . ^^^ Using mutational analysis of the CD 40 cytoplasmic tail , we demonstrate that the specific binding of TRAF 2 to CD 40 is required for efficient signaling on the NF kappaB , Jun N terminal protein kinase ( JNK ) , and p 38 axis . ^^^ In fibroblasts lacking TRAF 2 or in carcinoma cells in which TRAF 2 has been depleted by RNA interference , the CD 40 mediated activation of NF kappaB and JNK is significantly reduced , and the activation of p 38 and Akt is severely impaired . ^^^ Furthermore , we provide evidence that TRAF 6 regulates CD 40 signal transduction not only through its direct binding to CD 40 but also indirectly via its association with TRAF 2 . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Using a new method for gene targeting by homologous recombination in somatic cells , we produced and studied signaling by CD 40 and its viral oncogenic mimic , latent membrane protein 1 ( LMP 1 ) in mouse B cell lines lacking TRAF 1 , TRAF 2 , or both TRAFs . ^^^ In the absence of TRAF 1 , an increased amount of TRAF 2 was recruited to lipid rafts , and subsequently , more robust degradation of TRAF 2 and TRAF 3 was induced in response to CD 40 signaling . ^^^ Taken together , our findings indicate that TRAF 1 and TRAF 2 cooperate in CD 40 but not LMP 1 signaling and suggest that cellular levels of TRAF 1 may play an important role in modulating the degradation of TRAF 2 and TRAF 3 in response to signals from the TNFR superfamily . . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
Signaling via a CD 40 mutant that does not bind TNFR associated factor ( TRAF ) 1 , TRAF 2 , and TRAF 3 rescued B cells from CD 95 induced apoptosis . ^^^
Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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Interacting proteins: P25942 and Q12933 Pubmed SVM Score :0.0
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