| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.67525883 |
| These findings demonstrate that MUC 1 functions in cross talk between ErbB 2 and Wnt pathways by acting as a shuttle for HRG induced nucleolar targeting of gamma catenin . . 0.67525883^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.54099345 |
| However , several lines of evidence raised the possibility that the interaction between NDF and ErbB 2 involves another molecule , which belongs to the family of epidermal growth factor receptors . 0.54099345^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.63593095 |
| We show that in various cells ErbB 2 can form heterodimers with both EGF receptor ( ErbB 1 ) and NDF receptors ( ErbB 3 and ErbB 4 ) , suggesting that it may affect the action of heterologous ligands without the involvement of a direct ErbB 2 ligand . 0.63593095^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.54235501 |
| Analysis of a Neu differentiation factor ( NDF ) induced heterodimer between ErbB 3 and ErbB 2 favors a bivalence model ; the ligand simultaneously binds both ErbB 3 and ErbB 2 , but , due to low affinity of the second binding event , ligand bivalence drives dimerization only when the receptors are membrane anchored . 0.54235501^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :1.0861414 |
| Heterodimer interactions between HER 2 and HER 3 ( erbB 3 ) are activated by neu differentiation factor / heregulin ( HRG ) , and HER 2 / HER 3 heterodimers are constitutively activated in breast cancer cells with HER 2 gene amplification . 1.0861414^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| This still growing family of EGF related growth factors includes gp 30 , its homolog heregulin ( HRG ) , the rat homolog neu differentiation factor ( NDF ) , glial growth factors ( GLIA ) , ARIA and a 50 kDa factor from COLO 16 cells . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| ARIA acetylcholine receptor inducing activity protein , is a member of a family of ligands that includes the Neu differentiation factor , heregulin , and glial growth factor . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| ARIA , heregulin , neu differentiation factor , and glial growth factor are members of a new family of growth and differentiation factors whose effects have been assayed on Schwann cells , skeletal muscle cells , and mammary tumor cell lines . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Synapse associated expression of an acetylcholine receptor inducing protein , ARIA / heregulin , and its putative receptors , ErbB 2 and ErbB 3 , in developing mammalian muscle . ^^^ ARIA responsive myotubes expressed both erbB 2 and erbB 3 , but little EGFR / erbB1 or erbB 4 . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Chicken ARIA is homologous to the rat Neu differentiation factor and human here gulin , ligands for the receptor tyrosine kinase encoded by the neu ( c erbB 2 , HER 2 ) proto oncogene . ^^^ ARIA , a protein that stimulates acetylcholine receptor synthesis , is a member of the neu ligand family . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Recently we identified three novel Schwann cell mitogens named GGF ( glial growth factor ) 1 ( 34 kDa ) , GGF 2 ( 59 kDa ) , and GGF 3 ( 45 kDa ) , and provided evidence that they are three distinct but structurally related members of a larger family of factors , which includes heregulin , neu differentiation factor , and acetylcholine receptor inducing activity ( ARIA ) . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| The mRNA level of erbB 2 , erbB 3 , rapsyn , MuSK , SHP 2 and beta actin remained unchanged in response to ARIA stimulation in C2C12 cells . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| The neuregulins were originally discovered in searches for the acetylcholine receptor inducing activity ( ARIA ) , glial growth factor ( GGF ) , and a ligand for the oncogene neu ( ErbB2 / HER2 ) . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Neuregulins , identified originally as a potential ligand for erbB 2 ( Neu differentiation factor , NDF ) , stimulate proliferation of Schwann cells ( glial growth factor , GGF ) , increase the rate of AChR synthesis in cultured muscle cells ( AChR inducing activity ) and are expressed in motor neurons . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| In the absence of GGF signaling via erbB 2 receptors , radial glial development is abnormal . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| The neuregulin receptor proteins , erbB 2 and erbB 3 , are expressed on ensheathing and myelinating Schwann cells and rapidly phosphorylated with GGF treatment . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Human white matter from non neurologic cases , multiple sclerosis ( MS ) and other neurologic diseases ( OND , inflammatory and non inflammatory ) , was subjected to immunocytochemistry and Western blotting for expression of the neuregulin , glial growth factor 2 ( GGF 2 ) , and its receptors , erbB 2 , erbB 3 and erbB 4 . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| In 3 of 3 human rhabdomyosarcoma cell lines positive for both HER 2 and HER 3 receptors , the treatment with GGF 2 induced a significant increase in myogenic differentiation . . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| A 45 kilodalton protein heregulin alpha ( HRG alpha ) that specifically induced phosphorylation of p185erbB2 was purified from the conditioned medium of a human breast tumor cell line . ^^^ Scatchard analysis of the binding of recombinant HRG to a breast tumor cell line expressing p185erbB2 showed a single high affinity binding site [ dissociation constant ( Kd ) = 105 + / 15 picomolar ] . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| There was no significant association between AR , HRG , and CR 1 expression and nodal status , EGF receptor , or c erbB 2 protooncogene expression in these tumors . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Heregulin ( HRG ) has been described to bind to c erbB 3 / c erbB 4 and to stimulate c erbB 2 . ^^^ Here we describe the effects of HRG on cell growth and on ER and c erbB 2 expression in breast cancer cell lines containing distinct levels of c erbB 2 and ER ( BT 474 : c erbB 2 , ER+ ; MDA MB 361 : c erbB 2++ , ER++ ; MCF 7 : c erbB 2+ , ER ) . ^^^ Proliferation of estrogen stimulated , c erbB 2 and ER positive cells is inhibited by HRG in a dose dependent manner . ^^^ In the latter cells HRG efficiently blocks the estrogenic effect on c erbB 2 . ^^^ In MCF 7 cells , however , the inhibition of c erbB 2 can not be completely reverted by HRG . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| We also examined the mitogenic activity of NDF / HRG on MCF 10A cells that overexpress the erbB 2 receptor as a result of infection with a retroviral vector containing the human c erbB 2 gene ( MCF 10AerbB 2 cells ) . ^^^ These factors , known as the neu differentiation factors ( NDF ) or heregulins ( HRG ) , induce tyrosine phosphorylation of erbB 2 receptors as a result of their direct interaction with either erbB 3 or erbB 4 receptors . ^^^ Thus , NDF / HRG is a dual specificity growth factor for human mammary epithelial cells , and the responsiveness of the cells to NDF / HRG is influenced by the level of expression of erbB 2 receptors . . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| High expression of ErbB 2 is not sufficient to confer sensitivity towards the HRG ETA . ^^^ The human heregulins ( HRG ) and their rat counterparts ( neu differentiation factor , NDF ) have been identified as ligands for these receptors . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| In the presence of stimulatory concentrations of HRG , a blocking monoclonal antibody ( 2C4 ) to p185erbB2 is capable of significantly inhibiting phosphorylation of a 185 kDa protein as well as the subsequent incorporation of 3H thymidine within the human SC . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| We have tested the effects of antibodies against components of this system ( HRG beta 1 and p185erbB2 ) in cocultures of rat sensory neurons and human ( or rat ) Schwann cells to elucidate the role of these proteins in axon induced Schwann cell proliferation . 2C4 , a monoclonal antibody specific for the human p185erbB2 receptor tyrosine kinase , bound to the surface of human Schwann cells and reduced human Schwann cell incorporation of [ 3H ] thymidine by > 90 % compared with untreated controls in this coculture system . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| In biologically relevant systems , interaction of HRG with ErbB 3 or ErbB 4 results in the transactivation of ErbB 2 . ^^^ In this report , we show that ErbB 2 is a critical component in mediating HRG responsiveness in a panel of human breast and ovarian tumor cell lines . ^^^ HRG binding studies were performed with a panel of breast and ovarian tumor cell lines expressing a range of levels of ErbB 2 . ^^^ The biological responses to HRG were also compared to EGF and to the growth inhibitory anti ErbB 2 antibody , 4D5 . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Previously we reported that neu differentiation factor ( NDF ) / heregulin ( HRG ) elevates tyrosine phosphorylation of its receptors erbB 3 , erbB 4 , and erbB 2 ( through heterodimer formation ) . ^^^ We also showed that both NDF / HRG and antibodies to erbB 2 can arrest growth and induce differentiation in breast cancer cells . ^^^ We show that NDF / HRG and antibodies to erbB 2 receptors up regulate expression of p 53 by stabilizing the protein . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| HRG was found to potently induce the recruitment of the M ( r ) 85 , 000 regulatory subunit of PI3K by phosphotyrosine proteins in both nonneoplastic H16N 2 mammary epithelial cells ( which express normal c erbB 2 levels ) and in the 21MT 2 and 21MT 1 cell lines , which were all isolated from a single patient with intraductal and invasive ductal carcinoma of the breast and express c erbB 3 but not c erbB 4 in culture . ^^^ These data indicate that PI3K may be an especially important mediator of HRG induced proliferation in mammary epithelial cells and is involved in the autonomous proliferation of growth factor independent breast carcinoma cells with c erbB 2 gene amplification . . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| The discovery of the growth factor heregulin ( HRG ) has allowed us to investigate a number of biological events that are regulated by erbB 2 , 3 , and 4 signal transduction . ^^^ The biochemical and biological characteristics presented here demonstrate that overexpression of HRG induces morphological changes in MCF 7 cells as well as erbB 2 , erbB 3 , and erbB 4 autophosphorylation . ^^^ We observed that overexpression of HRG induces a more aggressive , hormone independent phenotype that is most likely directly related to the constitutive activation of the erbB 2 , erbB 3 , and erbB 4 receptor signaling cascade . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| The assay described in this report is able to specifically quantify tyrosine phosphorylation of ErbB 2 that results from the interaction of HRG with ErbB 3 and / or ErbB4 . . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Since erbB 2 , erbB 3 , and erbB 4 ( erbB 2 4 ) are often overexpressed in human breast cancer cells , we produced recombinant HRGs and a HRG based ligand toxin to investigate the signaling events triggered by HRGs and the ability of these ligands to specifically target such cells . ^^^ Recombinant HRG beta 2 stimulated the tyrosine phosphorylation of erbB 2 4 in ZR 75 1 human breast cancer cells . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| However , EGF and BTC were as effective as HRG in mediating signaling when ErbB 2 was co expressed with the chimera in the 32D . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| In overexpression cell systems , we demonstrate that HRG induced transformation by `` kinase impaired ' ' HER 3 is dependent on coexpression of kinase active HER 2 . ^^^ In cells coexpressing HER 2 and HER 4 , however , both kinases significantly contribute to the HRG induced mitogenic stimulus . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Cytotoxicity is dependent on high affinity binding of DT ( 389 ) hrg to HER 3 and HER 4 receptors and is not mediated by HER 2 overexpression alone . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Heregulin alpha ( HRG ) activates ErbB 2 in G8 / DHFR 3T3 cells by selectively inducing hetero oligomerization with kinase defective ErbB 3 , indicating that heterologous transphosphorylation is an unlikely prerequisite for ErbB 2 activation . ^^^ HRG also triggers association of epidermal growth factor receptors ( EGFR ) with a kinase inactive ErbB 2 subset while reducing EGFR association with active ErbB 2 . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Cells that do not express ErbB 4 but express ErbB 3 receptor , together with the ErbB 2 or EGFR , exhibited moderate sensitivity to HRG PE toxins . ^^^ HRG PE toxins have little or no activity against cells expressing EGFR , ErbB 2 , or ErbB 3 alone . ^^^ We conclude that there is therapeutic potential of HRG PE toxins in the therapy of cancers overexpressing the ErbB 4 or ErbB 2 plus ErbB 3 receptors . . ^^^ Recently , it has been shown that both ErbB 3 and ErbB 4 are receptors for heregulin ( HRG ) / Neu differentiation factor . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Although HRG can bind to ErbB 3 and ErbB 4 homodimers , the highest affinity and most intracellularly active receptor complexes are hetero oligomers containing ErbB 2 . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Cells expressing ErbB 3 alone display a single class of low affinity HRG binding sites , whereas both high and low affinity binding sites can be measured on cells that co express both ErbB 3 and ErbB 2 . ^^^ Further evidence for the unique specificity of ErbB 2 in generating this high affinity binding site was determined by inhibiting HRG binding with an ErbB 2 monoclonal antibody . . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Specific biological responses to the erbB 3 erbB4 ligand heregulin ( HRG ) have been postulated to be due to the formation of heterodimers of those receptors with erbB 2 . ^^^ To test the role that erbB 2 plays in the response to HRG in a human breast carcinoma cell line , antisense oriented erbB 2 was stably transfected into AU 565 cells . ^^^ In the absence of HRG , inhibition of erbB 2 expression slowed cell growth , leading to accumulation of cells in the G2 / M phase , and suppressed colony growth in soft agar . ^^^ Low concentrations of HRG induced cell proliferation in both the erbB 2 nonexpressing cells and the parental AU 565 cells . ^^^ In contrast , high concentrations of HRG failed to induce differentiation of the erbB 2 nonexpressing cells as compared with the parental cells . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| ErbB 3 was phosphorylated in vivo in response to either heregulin ( HRG ) in cells expressing both ErbB 3 and ErbB 2 , or epidermal growth factor ( EGF ) in cells expressing both ErbB 3 and EGF receptor . ^^^ Separate kinase inactivating mutations in the EGF receptor and ErbB 2 proteins abolished ErbB 3 phosphorylation and signal transduction activated by EGF and HRG respectively . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| We also demonstrated that HRG stimulation promoted physical interactions between PAK 1 , actin , and human epidermal growth factor receptor 2 ( HER 2 ) receptors , and these interactions were dependent on the activation of PI 3 kinase . ^^^ The blockade of HER 2 receptor by an anti HER 2 monoclonal antibody resulted in the inhibition of HRG mediated stimulation of PI 3 kinase / PAK pathway and also the formation of motile actin cytoskeleton structures but not extracellular signal regulated kinases . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| HRG can bind to receptor tyrosine kinases erbB 3 and erbB 4 , thereby inducing erbB 3 and erbB 4 heterodimerization with erbB 2 , leading to receptor tyrosine phosphorylation and activating downstream signal transduction . ^^^ 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: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| We have previously reported that Heregulin ( HRG ) / neu differentiation factor ( NDF ) induced growth arrest and cellular differentiation in breast cancer cells overexpressing erbB 2 receptor . ^^^ To elucidate the cellular mechanisms underlying the growth inhibition by HRG , we developed an in vitro model by transfection of HRG cDNA into the erbB 2 overexpressing breast cancer cell line , SKBr 3 . ^^^ In contrast , while HRG treatment of other erbB 2 overexpressing breast cancer cell lines led to growth arrest and cell detachment , it did not induce apoptotic features . ^^^ Thus , this study demonstrates that while growth arrest and cell detachment are general effects of HRG towards erbB 2 overexpressing cells , the ability of HRG to induce apoptosis is a phenomenon confined to selective cells including SKBr 3 cells . . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| These data demonstrate that HER 2 / neu overexpression itself affects the expression of other RTK 1 members and that cells expressing the highest levels of HER 2 / neu have the greatest response to HRG . . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Immunoprecipitation / Western blot studies revealed that HRG ( 100 ng / ml ) stimulated tyrosine phosphorylation and dimerization of ErbB 3 and ErbB 2 , but had no effect on phosphorylation of the EGFR . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| In our previous studies , heregulin ( HRG ) and anti HER 2 antibodies inhibited proliferation , increased invasiveness , and enhanced tyrosine autophosphorylation of SKBr 3 breast cancer cells that overexpressed HER 2 . ^^^ In the present report , the effects of HRG and anti HER 2 antibody have been compared in six ovarian cancer cell lines . ^^^ HRG inhibited anchorage independent growth of SKOv 3 cells that overexpressed HER 2 ( 10 ( 5 ) receptors / cell ) but stimulated the growth of OVCA 420 , OVCA 429 , OVCA 432 , OVCA 433 , and OVCAR 3 cells that expressed lower levels of the receptor ( 10 ( 4 ) receptors / cell ) . ^^^ Thus , cell lines with a high level of HER 2 relative to HER 3 or HER 4 were growth inhibited , whereas cell lines with lower levels of HER 2 were growth stimulated by HRG . ^^^ Stimulation or inhibition of clonogenic growth did not correlate with endogenous expression of HRG or with the impact of exogenous HRG on phosphorylation of HER 2 , HER 3 , or HER 4 . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Treatment of these cells with either MPA or HRG resulted in tyrosine phosphorylation of both ErbB 2 and ErbB 3 . ^^^ Furthermore , both HRG and MPA proliferative effects were abolished when cells were treated with ASODNs to ErbB 2 mRNA , providing evidence for a critical role of ErbB 2 in HRG induced growth . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| In a study of changes in gene expression initiated by HGF in Balb / MK keratinocytes , we observed the induction of Neu differentiation factor ( NDF ) mRNA ( also known as heregulin , or HRG ) . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Analyses of the members of the HRG stimulated complex revealed that RAFTK is associated with p 190 RhoGAP ( p 190 ) , RasGAP and ErbB 2 , and plays an essential role in mediating the tyrosine phosphorylation of p 190 by Src . ^^^ In addition , upon HRG stimulation of T47D cells , association of ErbB 2 with RAFTK was observed and found to be indirect and mediated by Src . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Remarkably HER 3 activation by HRG could occurs independent of HER 2 , and in one cell line almost no HER 4 activation by HRG was detected despite high levels expression . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| We have previously shown that HRG beta is mitogenic for various human mammary epithelial cell lines that coexpress c erbB 2 and c erbB 3 . ^^^ 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 . ^^^ The nontransformed H16N 2 cells isolated from normal tissue express EGFR , p 185 ( erbB 2 ) , and erbB 3 , and are highly responsive to the mitogenic effects of HRG beta as well as to the combination of EGF and insulin in serum free culture . ^^^ 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 . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Under conditions where co immunoprecipitation and cross linking of HER 2 and HER 3 were stimulated by hrg , HER 3 self association and cross linking were disrupted by hrg . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Therefore , the patterns of expression of the receptors , epidermal growth factor receptor ( EGF R ) , c erbB 2 , c erbB 3 , c erbB 4 , and one of the erbB ligands , heregulin ( HRG ) , were examined in normal and malignant breast cell lines and compared with expression of oestrogen receptor ( ER ) , a classical indicator of good prognosis . ^^^ A comparison of individual erbB receptors and HRG revealed that the majority of lines expressing increased levels of c erbB 2 also expressed elevated levels of c erbB 3 mRNA , and none of the cell lines that expressed both c erbB 2 and either c erbB 3 or c erbB 4 expressed the ligand HRG . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Western blot analysis showed activation of ErbB 2 and ErbB 3 , suggesting a possible mode of action of extracellular HRG in mammary gland carcinomas . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| A ligand for the erbB 2 receptor has not yet been identified but it can be activated by heterodimerization with heregulin ( HRG ) stimulated erbB 3 and erbB 4 receptors . ^^^ HRG expressing breast cancer cell lines are characterized by low erbB receptor levels and a high invasive and metastatic index , while those which overexpress erbB 2 demonstrate minimal invasive potential in vitro and are non tumorigenic in vivo . ^^^ Addition of exogenous HRG to non invasive erbB 2 overexpressing cells ( SKBr 3 ) at low concentrations induced formation of pseudopodia , enhanced phagocytic activity and increased chemomigration and invasion in the Boyden chamber assay . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| HRG binding induces ErbB 3 and ErbB 4 heterodimerization with ErbB 2 , activating downstream signal transduction . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| In studying whether neuregulins regulate glucose uptake in muscle , we analyzed the effect of a recombinant neuregulin , ( r ) heregulin beta 1 ( 177 244 ) ( HRG ) , on L6E9 muscle cells , which express the neuregulin receptors ErbB 2 and ErbB 3 . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| This result suggests that HRG may act through both HER 2 and c Src to facilitate anchorage independent growth . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Mice heterozygous ( + / ) for either heregulin ( HRG ) , ErbB 2 , or ErbB 3 were created by gene targeting , resulting in the loss of one functional gene copy and an associated decrease in targeted protein . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| In this study , we demonstrate that a naturally occurring secreted form of the human ErbB 3 receptor , p 85 soluble ErbB 3 ( sErbB 3 ) , is a potent negative regulator of heregulin ( HRG ) stimulated ErbB 2 , ErbB 3 , and ErbB 4 activation . ^^^ We show that p 85 sErbB3 binds to HRG with an affinity comparable to that of full length ErbB 3 and competitively inhibits high affinity HRG binding to ErbB2 / ErbB3 heterodimers on the cell surface of breast carcinoma cells with an IC ( 50 ) of 0 . 5 nM . p 85 sErbB3 inhibits HRG induced phosphorylation of ErbB 2 , ErbB 3 , and ErbB 4 in breast carcinoma derived cell lines and can also block HRG stimulated activation of mitogen activated protein kinase , Akt , and association of ErbB 3 with the phosphatidylinositol 3 ' kinase p 85 regulatory subunit . ^^^ The IC ( 50 ) for both p 85 sErbB3 and 2C4 ( a monoclonal antibody specific for ErbB 2 ) mediated inhibition of HRG binding is approximately 0 . 5 nM , although the mechanism of inhibition by these two proteins is distinct . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Heregulin ( HRG ) is one of the groups of polypeptide growth factors that activate the erbB 2 receptor via induction of heterodimerization with erbB 3 and erbB 4 receptors . ^^^ The vast majority of the reports indicate that HRG induces cell growth in breast cancer cells expressing normal levels of erbB 2 and growth inhibition and apoptosis in cells over expressing erbB 2 . ^^^ Previously we reported that constitutive expression of HRG in an erbB 2 overexpressing cell line ( SKBr 3 ) induced growth arrest and apoptosis . ^^^ This is a first report demonstrating that HRG induction of apoptosis is directly correlated with decreased MAPK activity , increased JNK activity resulting in upregulation of PEA 3 and down regulation of the erbB 2 receptor . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Furthermore , HRG induced colocalization and physical interaction of calnexin with the HER 2 growth factor receptor . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Our earlier studies have shown that recombinant heregulinbeta 1 ( HRG ) induces apoptosis in SKBr 3 breast cancer cells that overexpress HER 2 . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| However , expression of Gab 2 mutated at this site ( S159A Gab 2 ) not only enhanced HRG induced Gab 2 tyrosine phosphorylation and association with Shc and ErbB 2 , but also markedly increased tyrosine phosphorylation of ErbB 2 and other cellular proteins and amplified activation of the ERK and PKB pathways . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| HCT inhibited the ability of HRG to induce AMF expression in cells with a normal HER 2 level , and HCT mediated down regulation could be reversed by HRG treatment in breast cancer cells with a high HER 2 level . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| FAK associated with HER 2 only in response to 0 . 01 nM HRG . ^^^ In contrast , 1 nM HRG induced activation and increased association of tyrosine phosphatase SHP 2 with HER 2 but decreased association of HER 2 with FAK . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| G3BP induction , phosphorylation , ATPase activity , and relocalization after HRG treatment could all be blocked by pretreatment with the anti receptor HER 2 monoclonal antibody Herceptin ( trastuzumab ) , which may suggest additional applications for this therapeutic antibody . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Furthermore Erk activity was blocked by an antibody against HER 2 or by heregulin ( HRG ) depletion from the conditioned medium through immunoprecipitation . ^^^ In contrast , epidermal growth factor receptor ( Ab 528 ) antibody only blocked 10 20 % of E ( 2 ) induced Erk activation , suggesting that E ( 2 ) induced Erk activation is predominantly mediated through the secretion of HRG and activation of HER 2 by an autoctine / paracrine mechanism . ^^^ This evaluation of downstream signaling revealed that E ( 2 ) induced Erk activation is mediated by a HRG / HER 2 / PKC delta / Ras pathway that could be crucial for E ( 2 ) dependent growth promoting effects in early stages of tumor progression . . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| The transcriptional activity of the GADD 153 promoter as well as transcription from the C / EBP activating transcription factor ( ATF ) composite motif in the GADD 153 promoter was also stimulated by HRG inducible ATF 4 and activated HER 2 but not wild type HER 2 . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Heregulin ( HRG ) activates the ErbB 2 via induction of heterodimerization with ErbB 3 and ErbB 4 receptors . ^^^ Two nontransformed human mammary epithelial cell lines , the HB 2 and the HB 2 ( ErbB 2 ) ( the HB 2 engineered to overexpress ErbB 2 ) , displayed an opposite response to HRG mediated regulation . ^^^ HRG upregulated mRNA expression of COXII in the HB 2 cells , but suppressed COXII expression in the HB 2 ( ErbB 2 ) cells . ^^^ A human breast cancer cell line ( T47D ) , which expresses ErbB 2 at a level similar to that of the HB 2 cells , also responded to HRG by increasing COXII mRNA levels . ^^^ Therefore , HRG regulation of COXII expression depends on the levels of ErbB 2 expression . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Although LM 3 cells do not express HRG , they exhibit high levels of ErbB 2 and ErbB 3 as well as moderate expression of ErbB 4 . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| In this study , we compared the estrogenic action pattern of beta HCH to another ErbB 2 activating agent , heregulin beta 1 ( HRG ) , along with 17beta estradiol and epidermal growth factor , to understand the similarities and differences of their action mechanisms . ^^^ Immunocoprecipitation and Western blot studies indicated that beta HCH mainly promotes dimerization of ErbB 2 and ErbB 3 at early time points , whereas HRG causes their dimerization with a rapid and significant rise in their tyrosine phosphorylation levels . ^^^ These results indicate that , while both beta HCH and HRG act through ErbB 2 , their initial actions differ . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| To analyze whether there is a link between these two regulatory molecules , we studied the effects of ErbB 2 activation by heregulin ( HRG ) on BRCA 1 function . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| In order to assess the molecular mechanisms underlying PR transactivation by HRG , we blocked ErbB 2 expression in C4HD and T47D cells by using antisense oligodeoxynucleotides to ErbB 2 mRNA , which resulted in the abolishment of HRG ' s capacity to induce PR binding to a PRE , as well as CAT activity in the transient transfection assays . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| The growth factor heregulin ( HRG ) , expressed in about 30 % of breast cancer tumors , activates the erbB 2 receptor via induction of heterodimeric complexes of erbB 2 with erbB 3 or erbB 4 . ^^^ Our investigation into whether HRG is a factor likely to promote tumor formation independently of erbB 2 overexpression concludes that blockage of HRG expression suppresses the aggressive phenotype of MDA MB 231 breast cancer cells by inhibiting cell proliferation , preventing anchorage independent growth , and suppressing the invasive potential of the cells in vitro . ^^^ Our study is the first report and serves as a proof of the concept that HRG is a key promoter of breast cancer tumorigenicity and metastasis independently of erbB 2 overexpression and should be deemed a potential target in developing therapies for breast cancer . . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Heregulin ( HRG ) is an activator of the erbB 2 , erbB 3 and erbB 4 ( erbB 2 / 3 / 4 ) signaling pathway . ^^^ Transfection of full length HRG cDNA into the estrogen ( E 2 ) dependent cell line MCF 7 promoted an invasive E 2 independent phenotype , as well as persistent activation of the erbB 2 / 3 / 4 receptors . ^^^ Our data show that the HRG / M sequences are sufficient to sensitize MCF 7 cells to Doxo , and provide evidence that this sensitization is independent of erbB 2 activation . . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| In contrast to epidermal growth factor receptor or HER 2 , the kinasedeficient HER 3 self associates readily at low nanomolar concentrations and in the absence of its ligands , various isoforms of heregulin ( hrg ) . ^^^ Binding of hrg disrupts HER 3 oligomerization and leads to the formation of signaling competent heterodimers , preferentially with HER 2 . ^^^ High affinity binding of A 30 inhibits hrg dependent tyrosine phosphorylation of HER 2 and the hrg induced growth response of MCF 7 cells . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| We have investigated the protein expression pattern of the four ErbB receptors EGFR , Her 2 / neu , Her 3 and Her 4 , and correlated it with their putative ligands EGF , TGF alpha and HRG in 74 women with invasive breast cancer . ^^^ The co expression of EGFR / Her 3 was associated with the expression of all ligands , whereas the Her 2 / neu / Her 3 was correlated with HRG ( p = 0 . 002 ) , thereby indicating a functional relation between specific receptor dimer combinations and putative ligands . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Overexpression of human EGF receptor HER 2 ( erbB 2 ) leads to amplified heregulin ( HRG ) signaling , promoting more aggressive breast cancer that is nonresponsive to estrogen and the antiestrogenic drug tamoxifen . ^^^ The aim of this study was to investigate the impact of this HER 2 inhibitor on HRG induced signaling , proliferation , and sensitivity to tamoxifen in breast cancer cells with and without HER 2 overexpression . ^^^ The loss in signaling corresponded to downregulation of the HRG receptors , HER 3 and HER 4 , whereas HER 2 overexpression strongly stimulated the levels of both HRG receptors . ^^^ Although Hst blocked HRG signaling in both parental and HER 2 transfected cells , it enhanced sensitivity to tamoxifen only in the MCF 7 cells that overexpressed HER 2 . ^^^ These results suggest the potential use of Hst against HRG mediated growth of breast cancers with high and low levels of HER 2 and against tamoxifen resistance in HER 2 overexpressing breast cancer . . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Analysis of HER 2 transfected cells stimulated with heregulin beta 1 ( HRG ) revealed increased c Myc protein levels but not a corresponding increase in c Myc mRNA expression or any change in c Myc protein half life . ^^^ Transfection of HER 2 overexpressing cells with a construct containing the 5 ' untranslated region ( 5 ' UTR ) of c Myc mRNA originated from the P 2 promoter and placed upstream of the Renilla luciferase gene , enhanced reporter expression upon stimulation with HRG . ^^^ Together , these results demonstrate that HRG stimulation of HER 2 overexpressing cells leads to enhanced c Myc protein synthesis through activation of the PI3K / Akt / mTOR pathway and that the P2L of c Myc mRNA is the element responsible for induction of c Myc translation . . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| MCF 7 / HRG cells demonstrate constitutive hyperactivation of Her 2 / neu receptor as well as activation of down stream PI 3 ' K / AKT and MAPK signaling cascades . ^^^ A structural deletion mutant of HRG ( HRG M 4 ) lacking the N terminus sequence and the cytoplasmic transmembrane region of HRG was generated to investigate whether secretion of HRG and transactivation of Her 2 / neu actively contributed to HRG regulated p21WAF1 / CIP1 expression and cellular localization . ^^^ MCF 7 cells engineered to overexpress HRG M 4 did not demonstrate either activation of Her 2 / neu , PI 3 ' K / AKT , or MAPK . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| We studied epithelial expression of EGF , transforming growth factor a , amphiregulin , heregulin ( HRG ) , betacellulin ( BTC ) , and their receptors , EGFR , HER 2 , and HER 3 , by immunohistochemical analysis in resected bronchial tissue from 20 subjects with ( forced expiratory volume in 1 second [ FEV ( 1 ) ] < 75 % of predicted value ) and 18 without ( FEV ( 1 ) > 85 % predicted value ) COPD . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Using specific ErbB receptor inhibitors and depletion of receptors by RNA interference ( RNAi ) , we established that , surprisingly , activation of Rac by HRG is mediated not only by ErbB 3 and ErbB 2 but also by transactivation of EGFR , and it is independent of ErbB 4 . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| ErbB 2 is frequently coexpressed with ErbB 3 in breast cancer cells and in the presence of the ligand heregulin ( HRG ) the ErbB 2 / ErbB 3 receptors form a signaling heterodimer that can affect cell proliferation and apoptosis . ^^^ The major goal of the present study was to determine whether endogenous HRG causes autocrine / paracrine activation of ErbB 2 / ErbB 3 and contributes to the proliferation of mammary epithelial tumor cells . ^^^ Various mouse mammary cell lines also contained activated ErbB 2 / ErbB 3 and HRG transcripts . ^^^ It is likely that the secreted mature HRG activated the ErbB 2 / 3 receptors . ^^^ Treatment with HRG 1 siRNA oligonucleotides or infection with a retroviral construct to stably express HRG siRNA effectively reduced HRG protein levels , ErbB 2 / ErbB 3 activation , and the rate of proliferation , which could be reversed by the addition of HRG . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| METHODS : Using MCF 7 cells ( Her 2 + / ) engineered to overexpress heregulin ( MCF 7 / HRG ) , a ligand for the Her 2 / 3 / 4 network , we investigated whether HRG induced transactivation of Her 2 affected breast cancer cell sensitivity to chemotherapy and whether trastuzumab trigger receptor enhanced chemosensitivity ( REC ) when combined with chemotherapy without Her 2 overexpression . ^^^ Trastuzumab prevented activation of the antiapoptotic and proliferative cascades and inhibited HRG induced Her 2 / 3 phosphorylation . ^^^ Interestingly , HRG expression in tumor biopsies from invasive breast carcinomas ( n = 189 ) revealed that , whereas the minority ( 12 % ) of Her 2 positive tumors ( n = 60 ; 32 % ) demonstrated Her 2 phosphorylation , the majority ( 67 % ) of HRG overexpressing and Her 2 tumors ( n = 57 ; 30 % ) were in active Her 2 status . ^^^ CONCLUSION : We demonstrate that assessment of HRG expression and Her 2 activation define a particular breast cancer patient population for which trastuzumab plus CDDP or taxol are extremely efficient without Her 2 overexpression . . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| To address this problem , we use quantitative mass spectrometry to analyze dynamic effects of HER 2 overexpression on phosphotyrosine signaling in human mammary epithelial cells stimulated by epidermal growth factor ( EGF ) or heregulin ( HRG ) . ^^^ Data generated from this analysis reveal that EGF stimulation of HER 2 overexpressing cells activates multiple signaling pathways to stimulate migration , whereas HRG stimulation of these cells results in amplification of a specific subset of the migration signaling network . ^^^ Self organizing map analysis of the phosphoproteomic data set permitted elucidation of network modules differentially regulated in HER 2 overexpressing cells in comparison with parental cells for EGF and HRG treatment . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| We propose the name Neu differentiation factor ( NDF ) for p44 . . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| A partial amino acid sequence of the protein , termed Neu differentiation factor ( NDF ) , enabled cloning of the corresponding complementary DNA . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| We used molecular cloning and functional analyses to extend the family of Neu differentiation factors ( NDFs ) and to explore the biochemical activity of different NDF isoforms . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| ErbB 2 becomes rapidly phosphorylated and activated following treatment of many cell lines with epidermal growth factor ( EGF ) or Neu differentiation factor ( NDF ) . ^^^ The precise role of ErbB 2 in the transduction of the signals elicited by EGF and NDF is unclear . ^^^ We show that cell surface expression of ErbB 2 was selectively suppressed in these cells and that the activation of the mitogen activated protein kinase pathway and p70 / p85S6K , induction of c fos expression , and stimulation of growth by NDF were dramatically impaired . ^^^ We conclude that in T47D cells , ErbB 2 is a major NDF signal transducer and a potentiator of the EGF signal . ^^^ ErbB 2 becomes rapidly phosphorylated and activated following treatment of many cell lines with epidermal growth factor ( EGF ) or Neu differentiation factor ( NDF ) . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| The present report describes the participation in the neoplastic conversion of cph expressing ( 81C39 ) hamster fibroblasts of a hyperactive autocrine loop involving a neu differentiation factor [ NDF ] like protein . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| We show that beta forms of Neu differentiation factor ( NDF ) , homologous to acetylcholine receptor inducing activity , glial growth factor , and heregulin , prevent apoptotic death and stimulate DNA synthesis of the E 14 Schwann cell precursor , an early cell in the rat Schwann cell lineage . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| A 549 and A 427 lung adenocarcinoma cells treated with neu differentiation factor ( NDF ) showed increased erbB 2 phosphotyrosine staining , but to a much lesser extent than breast cancer cells . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| A technique using a biospecific affinity sensor , BIAcore , was applied to monitor and determine mammalian cell derived neu differentiation factor ( NDF ) in column fractions during chromatography . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Glycosylation trafficking , and regulated cleavage from the cell surface . new differentiation factor ( NDF ) , also known as heregulin , is structurally related to the epidermal growth factor family of growth factors ; it stimulates tyrosine phosphorylation of the neu / HER 2 oncogene and causes differentiation of certain human breast cancer cell lines . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| The extent of inhibition correlated with both receptor saturation and affinity of different NDF isoforms , and it was abolished upon overexpression of either EGF receptor or ErbB 2 . ^^^ Neu differentiation factor ( NDF , or heregulin ) and epidermal growth factor ( EGF ) are structurally related proteins that bind to distinct members of the ErbB family of receptor tyrosine kinases . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| No transcript of ErbB 4 was detectable in the keratinocytes , but these cells express multiple NDF mRNAs and also ErbB 2 . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| The folded peptide stimulates tyrosine phosphorylation of Her 2 , Her 3 and Her 4 in breast cancer cells and competes with low affinity with full length NDF alpha 2 for binding to the cells , while the linear one does not . ^^^ After several days treatment with NDF 5 or NDF alpha 2 , Her 2 transfected MCF 7 cells ( Her2 / MCF7 ) became similar morphologically to non transfected MCF 7 . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| We have analyzed the effects of Neu differentiation factor ( NDF ) / heregulin , a newly described activating ligand for erbB 2 and other members of the epidermal growth factor ( EGF ) receptor family , on cell growth and the expression of milk proteins in HC 11 cells . ^^^ In these cells , NDF induces tyrosine phosphorylation of erbB 2 and erbB 3 . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NDF stimulates tyrosine phosphorylation and the in vitro kinase activity of ErbB 2 . ^^^ When PKC is activated by TPA , NDF is no longer able to activate ErbB 2 in T47D cells , leading to a blockage of cell proliferation . ^^^ In summary , during growth or differentiation of mammary epithelial cells , NDF stimulates several independent signalling pathways which can also be triggered by ErbB 2 stimulation alone . ^^^ PKC activation blocks the biological effect induced by NDF through negative modulation of ErbB 2 . . ^^^ Neu differentiation factors ( NDF ) are a novel family of polypeptide factors which activate sub class 1 tyrosine kinase receptors . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Neu differentiation factor ( NDF ) is a 44 kD glycoprotein which was isolated from ras transformed rat fibroblasts and indirectly induces tyrosine phosphorylation of the HER 2 / neu receptor via binding to either the HER 3 or HER 4 receptor . ^^^ Since NDF , HER 2 / neu , and HER 3 are present in skin , and other EGF family members can influence wound keratinocytes in vivo , we investigated whether NDF would stimulate epidermal migration and proliferation in a rabbit ear model of excisional wound repair . ^^^ NDF alpha isoforms were expressed in dermal fibroblasts of wounded and unwounded skin , while both HER 2 / neu and HER 3 were expressed in unwounded epidermis and dermal adnexa . ^^^ Neu differentiation factor ( NDF ) is a 44 kD glycoprotein which was isolated from ras transformed rat fibroblasts and indirectly induces tyrosine phosphorylation of the HER 2 / neu receptor via binding to either the HER 3 or HER 4 receptor . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Expression vectors constructed from human and rat pro neu differentiation factor ( NDF ) cDNAs were transfected in Chinese hamster ovary cells for expression of recombinant NDF molecules . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Comparative analyses of both glycosylated and nonglycosylated neu differentiation factor ( NDF ) isoforms revealed significant similarities and differences of their overall structures and functions . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| The Neu differentiation factor ( NDF or heregulin ) , however , also acts as a mitogen for epithelial , Schwann and glial cells . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| This protein , termed Neu differentiation factor ( NDF ) , is derived from a transmembrane precursor that contains an EGF like motif and an immunoglobulin like domain . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Neu differentiation factor ( NDF , also called heregulin ) was isolated from mesenchymal cells on the basis of its ability to elevate phosphorylation of ErbB proteins . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Neu differentiation factor ( NDF / heregulin ) is a 44 kDa glycoprotein that interacts with the Neu / ErbB 2 receptor tyrosine kinase to increase its phosphorylation on tyrosine residues . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Cell type specific interaction of Neu differentiation factor ( NDF / heregulin ) with Neu / HER 2 suggests complex ligand receptor relationships . ^^^ A 44 kDa glycoprotein that elevates tyrosine phosphorylation of Neu has been isolated and named Neu differentiation factor ( NDF ) , or heregulin . ^^^ Here we show that NDF affects tyrosine phosphorylation of Neu in human tumor cells of breast , colon and neuronal origin , but not in ovarian cells that overexpress the receptor . ^^^ Nevertheless , unlike breast derived Neu , the ovarian protein did not display covalent cross linking to radiolabeled NDF , and was devoid of ligand induced association with phosphatidylinositol 3 ' kinase . ^^^ Similar to the endogenous receptor , the ectopically overexpressed Neu of mammary cells , but not of ovarian and fibroblastic cells , exhibited elevated levels of NDF induced phosphorylation and covalent cross linking of the radiolabeled factor . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Neu differentiation factor ( NDF , also called heregulin ) is a 44 kilodalton glycoprotein that stimulates tyrosine phosphorylation of the Neu / HER 2 receptor and induces phenotypic differentiation of certain mammary cancer cell lines to growth arrested and milk producing cells . ^^^ Taken together , our observations suggest that the induction of ICAM 1 by NDF may affect the morphology , differentiation state , and metastasis of Neu expressing mammary tumor cells . . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NDF induced phosphorylation of ErbB 2 and ErbB 3 was found in the breast epithelial cell line MCF10A , the breast tumor cell lines T47D and MCF 7 , and the ovarian tumor cell line OVCAR 3 . ^^^ Efficient NDF induced phosphorylation of ErbB 3 was strictly ErbB 2 dependent in the breast tumor cell lines T47D and MCF 7 , while it was largely ErbB 2 independent in MCF10A and OVCAR 3 cells . ^^^ Consequently , NDF stimulated intracellular signaling and induction of a biological response displayed a cell specific requirement for ErbB 2 . ^^^ Thus , while ErbB 2 cooperates with NDF receptors in the breast tumor cell lines , ErbB 2 independent mechanisms seem to prevail in other cellular contexts . . ^^^ Neu differentiation factor ( NDF ) induced signaling involves the activation of members of the ErbB family of receptor tyrosine kinases . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| In order to explore the signal transduction pathways potentially activated by NDF , we examined expression of the receptors erbB 2 , erbB 3 and erbB 4 in mammary epithelial cells established from an NDF induced tumor . ^^^ Neu differentiation factor ( NDF ) , a member of the neuregulin family of ligands of erbB receptors , induces both differentiative and mitogenic effects on cultured human mammary epithelial cells . ^^^ Since members of the epidermal growth factor receptor family , including Neu / erbB2 , have been implicated in mammary carcinoma , we wished to know whether a potential ligand of this family , NDF , could induce such effects in the mammary gland in vivo . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| While several EGF agonists bind and activate ErbB 1 / EGF receptor , neu differentiation factor ( NDF ) functions as a ligand for ErbB 3 and ErbB 4 . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| The group of subtype 1 transmembrane tyrosine kinases includes the epidermal growth factor ( EGF ) receptor ( ErbB 1 ) , an orphan receptor ( ErbB 2 ) , and two receptors for the Neu differentiation factor ( NDF / heregulin ) , namely : ErbB 3 and ErbB 4 . ^^^ By using the generated mAbs , we found that the major NDF receptor on mammary epithelial cells is a heterodimer of ErbB 3 with ErbB 2 , whereas an ErbB 1 / ErbB 2 heterodimer , or an ErbB 1 homodimer , is the predominant species that binds EGF . ^^^ Consistent with ErbB 2 being a shared receptor subunit , its tyrosine phosphorylation was increased by both heterologous ligands and it mediated a trans inhibitory effect of NDF on EGF binding . ^^^ These results suggest that homodimers of ErbB 4 are biologically active , but heterodimerization of the kinase defective ErbB 3 , probably with ErbB 2 , is essential for transmission of NDF signals through ErbB 3 . . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| However , NDF induced cell transformation was observed when either HER 1 or HER 2 was coexpressed with HER 3 or HER 4 . ^^^ To assess the role of receptor heterodimerization , we analyzed the ability of Neu differentiation factor ( NDF ) to induce cell growth and transformation of NIH 3T3 cells transfected with different combinations of the EGFR subfamily of receptors . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| The ErbB family of transmembrane tyrosine kinases includes the receptor for EGF ( ErbB 1 ) , two receptors for NDF / heregulin ( ErbB 3 and ErbB 4 ) and an orphan receptor ( ErbB 2 ) . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Both groups bind to the catalytically impaired receptor tyrosine kinase ErbB 3 , whose mitogenic stimulation by NDF requires transactivation by other ErbB proteins , either ErbB 1 or ErbB 2 . ^^^ These results imply that NDF isoforms differ in their ability to induce receptor heterodimers ; whereas both types of isoforms signal through ErbB 3 / ErbB 2 heterodimers , only beta isoforms are able to stabilize ErbB 3 / ErbB 1 heterodimers . . ^^^ The multiple isoforms of Neu differentiation factor ( NDF / neuregulin ) induce a pleiotropic cellular response that is isoform specific and cell type dependent . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| This study compares changes in the phenotype of cultured Schwann cells after exposure to the cytokine tumor necrosis factor ( TNF ) alpha or the mitogen neu differentiation factor ( NDF ) beta . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Consistent with this view , we now report that there is a dramatic differential response of Schwann cells to the two major isoforms of neu differentiation factor ( NDF alpha and NDF beta ) . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| By utilizing reverse transcriptase polymerase chain reaction ( RT PCR ) methodology , we have detected the messenger RNA encoding the protein of the neu gene ( p185neu ) and Neu differentiation factor ( NDF ) isoforms in the olfactory mucosa . ^^^ The presence of neu and NDF transcripts in the olfactory tissue and the localization of their encoded polypeptides to proliferative regions of the epithelium suggest involvement of these gene products in the regulated proliferation / differntiation of the sensory neurons . . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Both , erbB 4 and its ligand , neu differentiation factor ( NDF ) / heregulin family , have been reported to be expressed abundantly in nervous system . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| METHODS : Expression of NDF , HER 2 , HER 3 , and HER 4 was studied in 24 frozen prostatectomy specimens by immunohistochemistry . ^^^ In spite of displaying NDF mRNA , prostate cancer cells do not produce detectable NDF protein , but express HER 2 and HER 3 proteins . ^^^ The ligand for these receptors and another related family member , HER 4 , has recently been identified by independent investigator groups and called neu differentiation factor ( NDF ) or heregulin . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| An apoptosis inducing isoform of neu differentiation factor ( NDF ) identified using a novel screen for dominant , apoptosis inducing genes . ^^^ Using this assay , we isolated a novel isoform of the proto oncogene Neu differentiation factor ( NDF ) , a ligand for erbB receptor tyrosine kinases . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Down regulation of cell surface ErbB 1 or ErbB 2 by intracellular expression of specific antibodies has allowed us to delineate the role of these receptors during signaling elicited by : EGF and heparin binding EGF ( HB EGF ) , ligands of ErbB 1 ; betacellulin ( BTC ) , a ligand of ErbB 1 and ErbB 4 ; and neu differentiation factor ( NDF ) , a ligand of ErbB 3 and ErbB 4 . ^^^ NDF activated ErbB 3 or ErbB 4 heterodimerize with ErbB 1 only when no ErbB 2 is available . ^^^ If all ErbB receptors are present , NDF receptors preferentially dimerize with ErbB 2 . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| ErbB 2 is an orphan receptor that belongs to a family of tyrosine kinase receptors for either epidermal growth factor ( EGF ) or Neu differentiation factor ( NDF / neuregulin ) . ^^^ One group of tumor inhibitory mAbs ( Class 2 mAbs ) was elicited by the most antigenic site of ErbB 2 , and inhibited in trans binding of NDF and EGF to their direct receptors . ^^^ The inhibitory effect was due to acceleration of ligand dissociation , and it resulted in the reduction of the ability of ErbB 2 to transactivate the mitogenic signals of NDF and EGF . ^^^ ErbB 2 is an orphan receptor that belongs to a family of tyrosine kinase receptors for either epidermal growth factor ( EGF ) or Neu differentiation factor ( NDF / neuregulin ) . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Neu differentiation factor ( NDF ) , a member of the epidermal growth factor ( EGF ) related peptide family , activates ErbB 2 via heterodimerization with the NDF receptors ErbB 3 and ErbB 4 . ^^^ In this paper , we show that the ErbB 2 overexpressing breast tumor cells SKBR 3 , AU 565 , and MDA MB 453 are growth inhibited by NDF . ^^^ Cells with elevated levels of ErbB 2 but little or no NDF receptors ( SKOV 3 and MDA MB 361 ) or cells with low levels of ErbB 2 ( T47D and MCF 7 ) are not growth inhibited . ^^^ In addition , NDF caused a down regulation of ErbB 2 but not of ErbB 3 . ^^^ Neu differentiation factor ( NDF ) , a member of the epidermal growth factor ( EGF ) related peptide family , activates ErbB 2 via heterodimerization with the NDF receptors ErbB 3 and ErbB 4 . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Recent evidence has suggested that neu differentiation factor ( NDF ) , which is a member of the neuregulin family of growth factors , influences the development of glial cells , including Schwann cells , astrocytes , and OLGs . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| LNCaP stimulated with NDF demonstrated crosstalk between ErbB 3 and ErbB 2 which did not involve ErbB 1 . ^^^ Interestingly , while TGF alpha was expressed in the majority of PCA lines , the ligand Neu Differentiation Factor / Heregulin ( NDF ) was expressed only in an immortalized , non transformed prostate epithelial line . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Previous studies have suggested that neu differentiation factor ( NDF ) , a member of the neuregulin ( NRG ) family of growth factors , may regulate the development of PNS and CNS glial cells . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Neu differentiation factor ( NDF / neuregulin ) is widely expressed in the central and peripheral nervous systems , where it functions as a mediator of the interactions between nerve cells and Schwann , glia , oligodendrocyte , and muscle cells , to control cellular proliferation , differentiation , and migration . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Furthermore , the neuroregulin of glial origin neu differentiation factor ( NDF ) was found to facilitate the action of TGF alpha , suggesting that other growth factors may exert their biologic effects on GnRH neuronal function via a glia / neuron interaction . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Neu differentiation factor ( NDF ) is a member of the epidermal growth factor ( EGF ) family of growth factors and is represented by multiple conserved isoforms . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| We reported previously that expression of the cph oncogene in Syrian hamster and mouse cells leads to the secretion of a polypeptide factor or factors structurally and functionally related to neu differentiation factor ( NDF ) and the establishment of an autocrine loop mediated through the simultaneous overexpression of the erbB 4 receptor . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Neu differentiation factor ( NDF ) / heregulin activates ErbB 2 via heterodimerization with the NDF receptors ErbB 3 and ErbB 4 . ^^^ Cells which express normal levels of these receptors are often growth stimulated by NDF , whereas SKBR 3 , and other ErbB 2 overexpressing breast tumour cells are growth inhibited . ^^^ Neu differentiation factor ( NDF ) / heregulin activates ErbB 2 via heterodimerization with the NDF receptors ErbB 3 and ErbB 4 . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Using the MCF 10A breast epithelial cell line , we observed that induction of overexpression of ornithine decarboxylase ( ODC ) ( the first rate limiting enzyme in polyamine biosynthesis ) markedly potentiated the anchorage independent growth stimulating effect of the beta 2 isoform of neu differentiating factor ( NDF ) known to activate HER 2neu in MCF 10A cells . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Concentrating on ErbB 1 and two of its ligands , epidermal growth factor ( EGF ) and transforming growth factor alpha ( TGF alpha ) , and the Neu differentiation factor ( NDF / neuregulin ) and one of its receptors , ErbB 3 , we show that ligand binding variably accelerates endocytosis of the respective ligand receptor complex . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| This model system allowed the comparison of EGF activated ErbB 1 with ErbB 1 activated by Neu differentiation factor ( NDF ) induced heterodimerization with ErbB 4 . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| A Neu differentiation factor ( NDF ) domain essential for proliferation and alterations in morphology of colonic epithelial cells in vitro . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Neu differentiation factor ( NDF ) , a dominant oncogene , causes apoptosis in vitro and in vivo . ^^^ Neu differentiation factor ( NDF , also called neuregulin ) is a potent inducer of epithelial cell proliferation and has been shown to induce mammary carcinomas in transgenic mice . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Neu differentiation factor ( NDF ) , a 44 kD polypeptide , is a member of the neuregulin family which also includes glial growth factor , heregulin and acetylcholine receptor inducing activity . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Here , we report that human colorectal cancer cell lines express abundant levels of HER 2 and HER 3 receptors , and are growth stimulated by recombinant neu differentiation factor beta 1 ( NDF ) . ^^^ NDF treatment of colorectal cancer cells was accompanied by increased tyrosine phosphorylation and heterodimerization of HER 3 with HER 2 . ^^^ In addition , we demonstrated that HER 2 and HER 3 receptors in colorectal cancer cells are constitutively phosphorylated on tyrosine residues and form heterodimeric complexes in the absence of exogenous NDF . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Our observations provide evidence for the following : recombinant human neu differentiation factors ( NDFbeta 1 , 2 and 3 ) are mitogenic to OBECs ; the activity in ACM can be neutralized by NDF antibodies ; these same antibodies detect a 50 kDa , non heparin binding protein in concentrated ACM ; astrocytes express detectable nrg 1 transcripts ; and OBECs express functional NRG receptors erbB 2 and erbB4 . . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Neu differentiation factor ( NDF ; also known as neuregulin ) induces a pleiotropic cellular response that is cell type dependent . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Here , we report that the neuregulin neu differentiation factor ( NDF ) increases the expression of tau mRNA and tau protein in OLGs . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| A2 tumor cells with HER 2 receptor agonists ( EGF and NDF ) enhanced tumor ability to activate CTL from tumor associated lymphocytes ( TAL ) and from T cells from peripheral blood in vitro . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Among representative NRG 1 isoforms , neu differentiation factor ( NDF , type 1 ) is expressed in the female reproductive tract and is localized to the implantation site . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Her 2 neu positivity predicted for NDF and CSS on multivariate analysis . ^^^ Projected 5 year freedom from NDF was 70 % for Her 2 neu positive and 97 % for Her 2 neu negative patients ( P < 0 . 01 , log rank ) . ^^^ CONCLUSIONS : Her 2 neu amplification predicts development of NDF and negatively influences CSS , but not local control or OS in elderly patients treated with breast conservation . ^^^ Her 2 neu positivity predicted for NDF and CSS on multivariate analysis . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| The biological effects of NRG 1 are mediated by receptor tyrosine kinases ErbB 2 , ErbB 3 , and ErbB 4 . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Unexpectedly , mice with loss of function mutations of NRG 1 or of either of two of their cognate receptors , ErbB 2 and ErbB 4 , die during midembryogenesis due to the aborted development of myocardial trabeculae in ventricular muscle . ^^^ Neuregulins ( i . e . neuregulin 1 ( NRG 1 ) , also called neu differentiation factor , heregulin , glial growth factor , and acetylcholine receptor inducing activity ) are known to induce growth and differentiation of epithelial , glial , neuronal , and skeletal muscle cells . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Specifically , NRG 2 alpha [ corrected ] , like NRG 1 beta [ corrected ] , emerges as a narrow specificity ligand , whereas NRG 2 beta [ corrected ] is a pan ErbB ligand that binds with different affinities to all receptor combinations , including those containing ErbB 1 , but excluding homodimers of ErbB 2 . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Two of the neuregulins ( NRG 1 and NRG 2 ) and their receptors ( erbB 2 and erbB 4 ) are essential for normal cardiac development and can mediate hypertrophic growth and enhance survival of embryonic , postnatal , and adult rat ventricular myocytes . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Although expression of NRGs and their receptors declines after midembryogenesis , both ErbB 2 and ErbB 4 are present in cardiac myocytes , and NRG 1 expression remains inducible in primary cultures of coronary microvascular endothelial cells from adult rat ventricular muscle . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| To evaluate this possibility , we constructed a series of HER targeted gene transfer vehicles by covalently linking poly L lysine polymers ( pLYS ) to the epidermal growth factor like domain of the HER ligand neuregulin 1 ( NRG 1 ( 177 244 ) ) , a HER 2 antibody ( Ab ) , and the Fab fragment of the HER 2 Ab . ^^^ In cell lines engineered to solely express HER 2 , HER 3 , or HER 4 , each vehicle correctly targeted the receptors ; the NRG 1 ( 177 244 ) construct transferred a luciferase gene only into cells expressing HER 4 , whereas the HER 2 Ab and Fab constructs transferred the reporter gene only into cells expressing HER 2 . ^^^ The most efficient gene transfer occurred using the intact HER 2 Ab as a gene transfer vehicle , whereas the Fab fragment of the HER 2 Ab was the least efficient , and NRG 1 ( 177 244 ) was intermediate . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Following deafferentation , the expression of erbB 4 , erbB 2 and neuregulin 1 ( NRG 1 ) mRNAs in the OB was altered . ^^^ At early stages ( 7 14 days ) after lesion the levels of expression of olfactory marker protein ( OMP ) , tyrosine hydroxylase ( TH ) , erbB 4 and NRG 1 mRNAs were decreased , whilst expression of erbB 2 increased and that of NRG 2 was not significantly altered . ^^^ At day 28 after the lesion , when olfactory receptor neuron axons had reinnervated the olfactory bulb , the expression levels of OMP , TH , erbB 2 , erbB 4 and NRG 1 were identical to control values . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Here we show that the activation of PPARgamma through the 15 deoxy Delta 12 , 14 prostaglandin J ( 2 ) ( PG J ( 2 ) ) ligand causes a dramatic inhibition of ErbB 2 and ErbB 3 tyrosine phosphorylation caused by neuregulin 1 ( NRG 1 ) and neuregulin 2 ( NRG 2 ) in MCF 7 cells . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| On the basis of our previous studies with recombinant neuregulin 1beta ( NRG 1beta ) , a ligand for the erbB 2 receptor tyrosine kinase , we hypothesized that activation of erbB 2 by anti erbB 2 versus NRG 1 would cause differential effects on myocyte intracellular signaling as well as anthracycline induced myofibrillar injury and might potentially account for the clinical toxicity of trastuzumab in the setting of concurrent anthracycline therapy . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| In contrast to previously characterized chimeras of EGF with NRG 1 or TGF alpha , these variants did not only show high binding affinity for ErbB 2 / ErbB 3 heterodimers but also for ErbB 3 alone . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Inhibition of HER 2 ' s ability to dimerize using the HER 2 specific antibody 2C4 completely blocked NRG 1 induced JAK 3 , TYK 2 , STAT 3 , and STAT 5 tyrosine phosphorylation . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Given these NRG 1 actions , we hypothesized that the synaptic loss , gliosis , inflammation , and neuronal death occurring in Alzheimer disease ( AD ) is associated with altered expression of NRG 1 and its receptors ( the erbB 2 , erbB 3 , and erbB 4 membrane tyrosine kinases ) . ^^^ All 4 molecules are associated with neuronal cell bodies , but only NRG 1 , erbB 2 , and erbB 4 are present in synapse rich regions . ^^^ NRG 1 and erbB 4 , as well as erbB 2 , are similarly associated with neuritic plaques in the doubly transgenic mice . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Down regulation of expression and activity of erbB 2 , a member of the NRG 1 receptor complex , leads to the transformation of radial glial cells into astrocytes . ^^^ These results suggest that developmental changes in NRG 1 erbB 2 interactions modulate the establishment of radial glia and contribute to their appropriate transformation into astrocytes . . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Relative to nontransformed Schwann cells , JS 1 cells overexpress the NRG 1 receptor erbB 3 and its erbB 2 coreceptor ; JS 1 erbB2 transcripts show no evidence of the activating mutation commonly found in N ethyl N nitrosourea induced neoplasms . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| ErbB 2 and erbB 3 receptors , which transduce the NRG 1 signal in Schwann cells , were found throughout the cytoplasm and in the processes and were also localized in the cell nucleus . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Our prior studies identified co expression of the human epidermal growth factor like receptors 2 ( ErbB 2 ) and 3 ( ErbB 3 ) , as well as the growth factor neuregulin 1 ( NRG 1 ) in normal lung epithelium and lung cancers . ^^^ As ErbB 2 and ErbB 3 dimerize to produce a high affinity receptor for NRG 1 , we postulated that an autocrine growth loop was present in transformed and non transformed pulmonary epithelial cells . ^^^ To test this hypothesis , we examined four cell lines derived from human non small cell carcinomas for : ( 1 ) ErbB 2 and ErbB 3 expression and endogenous activation ; ( 2 ) NRG 1 expression and secretion / shedding ; and ( 3 ) the effect of receptor blockade on autocrine receptor activation . ^^^ Basal ErbB 2 phosphorylation was identified in all lung cancer cell lines and was inhibited with an antibody that blocked the NRG 1 binding site on ErbB 3 . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| To test this hypothesis , we examined the expression of the NRG 1 receptor subunits erbB 2 , erbB 3 , and erbB 4 in rat lumbar DRG and spinal cord . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| We found that NRG 1 is expressed by spiral ganglion neurons ( SGNs ) , whereas erbB 2 and erbB 3 are expressed by supporting cells of the organ of Corti , suggesting that these molecules mediate interactions between these cells . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Previous studies showed that NRG 1 induced HER 2 activation resulted in pulmonary epithelial cell proliferation in the human fetal lung . ^^^ In the present study , the authors show that NRG 1 , HER 2 , and HER 3 , but not HER 4 , are expressed in the developing mouse lung . ^^^ This increase in branching was blocked by 2C4 , an antibody directed against HER 2 that inhibits its dimerization and subsequent NRG 1 induced signal transduction . ^^^ These data suggest that NRG 1 , binding to the HER2 / HER3 heterodimer receptor complex , induces pulmonary branching morphogenesis through HER 2 activation of the PI3K pathway . . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NRG 1beta effects on neurite extension and arborization are similar to , but not additive with , those of brain derived neurotrophic factor and reflect direct NRG 1 action on hippocampal neurons as these cells express the NRG 1 receptors erbB 2 and erbB 4 , the erbB specific inhibitor PD 158780 decreases NRG 1beta induced neurite outgrowth , and NRG 1beta stimulation induces p42 / 44 ERK phosphorylation . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| LV protein levels of NRG 1 , erbB 2 , and erbB 4 receptors were similar in WT Dox and NRG 1 ( + / ) Dox mice . ^^^ However , levels of phosphorylated erbB 2 , Akt , and ERK 1 / 2 were significantly decreased in NRG 1 ( + / ) Dox compared with WT Dox mice . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Neoplastic Schwann cells within these neoplasms variably express the erbB kinases mediating NRG 1 responses ( erbB 2 , erbB 3 and / or erbB 4 ) . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Because previous studies showed that alpha ( 2a 2b ) NRG 1 is overexpressed at early stages along the muscle vein combined tubes , we have also investigated mRNA expression of its two receptors , erbB 2 and erbB 3 . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| We have previously shown that VSs produce the glial growth factor , neuregulin 1 ( NRG 1 ) , and its receptors , ErbB 2 and ErbB 3 . ^^^ We confirm that human VSs , which express markers of immature and denervated SCs , also express endogenous NRG 1 and activated ErbB 2 . ^^^ We find that a blocking anti NRG 1 antibody and trastuzumab ( Herceptin , HCN ) , a humanized anti ErbB 2 inhibitory monoclonal antibody , effectively inhibit NRG 1 induced SC proliferation . ^^^ |
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| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Neoplastic Schwann cells almost uniformly express erbB 2 and erbB 3 , 2 membrane receptor tyrosine kinases mediating NRG 1 and NRG 2 action . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| In the present study , we have investigated to what extent ErbB 2 , the favored co factor of ErbB 4 for heterodimerization , participates in the cardiac effects of endothelium derived NRG 1 . ^^^ CMVE derived NRG 1 was shown to phosphorylate cardiomyocyte ErbB 2 , an event prevented by a 24 h preincubation of myocytes with monoclonal ErbB 2 antibodies . ^^^ Accordingly , ErbB 2 signaling participated in the paracrine survival and growth controlling effects of NRG 1 on cardiomyocytes in vitro , explaining the cardiotoxicity of ErbB 2 antibodies in patients . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| BACE 1 / mice displayed hypomyelination of peripheral nerves and aberrant axonal segregation of small diameter afferent fibers , very similar to that seen in mice with mutations in type 3 NRG 1 or Schwann cell specific ErbB 2 knockouts . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| Mammalian cell expressed SMDF activates tyrosine phosphorylation of a 185 kDa protein in cell lines expressing p185erbB2 , indicating that it is biologically active . ^^^ |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P04626 |
Pubmed |
SVM Score :0.0 |
| NA |
|