Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :1.1016965
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 . 1.1016965^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
ARIA responsive myotubes expressed both erbB 2 and erbB 3 , but little EGFR / erbB1 or erbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Accordingly , cytotoxicity assays were performed on NIH / 3T3 cell lines transfected with EGFR , ErbB 2 , ErbB 3 , or ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
A neu acquaintance for erbB 3 and erbB 4 : a role for receptor heterodimerization in growth signaling . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Cross linking experiments showed binding of HRGbeta 1 to ErbB 3 but not ErbB 2 or ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
We show that erbB 2 , erbB 3 and erbB 4 are concentrated at synaptic sites in adult skeletal muscle . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Both erbB 2 and erbB 3 , but not erbB 4 , were expressed in cultured mouse keratinocytes and in mouse epidermis in vivo . ^^^
Interacting proteins: Q15303 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: Q15303 and P04626	Pubmed	SVM Score :0.0
While ErbB1 / EGFR , ErbB2 / NEU , and ErbB 3 were always observed in a distinct pattern , ErbB 4 was not observed . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
These include EGF receptor ( erbB 1 ) and erbB 4 when expressed individually and erbB 2 and erbB 3 when expressed together . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Unlike the EGFR and erbB 2 relatively little is known about the expression of erbB 4 in human tumours . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Other members are ErbB 2 , ErbB 3 , and ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Our ALISA does not detect full length ErbB 2 , ErbB 3 , or ErbB 4 ; or p 105 soluble ErbB 2 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Epidermal growth factor ( EGF ) receptor tyrosine kinases include ErbB 1 , ErbB 2 , ErbB 3 and ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Neuregulin stimulates ErbB 2 , ErbB 3 , and ErbB 4 , members of the ErbB family of receptor tyrosine kinases . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
High levels of ErbB 2 and ErbB 3 expression and low ErbB 4 levels were found in HD cells . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
We demonstrate that ErbB 2 ( neu ) , ErbB 3 , and ErbB 4 are highly expressed , whereas ErbB 1 ( EGF r ) is undetectable . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Our antiestrogen resistant cell lines did not express altered levels of EGFR , HER 2 / neu , ErbB 3 , or ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
All forms of NRGs contain an EGF like domain that is sufficient to activate NRG receptors erbB 2 , erbB 3 , and erbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
An immunohistochemical analysis indicates that NCC express erbB 2 and erbB 4 neuregulin receptors . . ^^^
Interacting proteins: Q15303 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: Q15303 and P04626	Pubmed	SVM Score :0.0
The fatty acid enhanced the tyrosine phosphorylation of ErbB 4 but not of ErbB 2 or ErbB 3 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The length of RT PCR products were 380 bp for erbB 1 , 500 bp for erbB 2 , 644 bp for erbB 3 , and 416 bp for erbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
RESULTS : The expression profiles demonstrated varying levels of EGFR , ErbB 2 , ErbB 3 , and ErbB 4 expression . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Cultured SGSCs express the neuregulin receptors ErbB 2 and ErbB 3 , but not ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Heregulin ( HRG ) activates the ErbB 2 via induction of heterodimerization with ErbB 3 and ErbB 4 receptors . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The ErbB family of receptor tyrosine kinases comprise four members : EGFR , ErbB 2 , ErbB 3 and ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
ErbB 2 is a ligand less member of the ErbB receptor family that functions as a coreceptor with EGFR , ErbB 3 , and ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Then we transfected erbB 2 gene into MDA MB 435 and found the induction of erbB 3 expression but not erbB 1 and erbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
EGFR is a member of the ErbB family of receptors which also includes ErbB 2 , ErbB 3 , and ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
BTC induced phosphorylation of all three EGF receptors present on HUVECs : ErbB 2 , ErbB 3 , and ErbB 4 . ^^^
Interacting proteins: Q15303 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 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
We now report that RALT binds to ligand activated epidermal growth factor receptor ( EGFR ) , ErbB 4 and ErbB 2 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
BTC induced phosphorylation of all four EGF receptors present on HTASMCs : ErbB 1 , ErbB 2 , ErbB 3 , and ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
No overexpression of erbB 2 , erbB 3 or erbB 4 was detected . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
MIA PaCa 2 and BxPC 3 protein lysates were probed with antibodies to EGFR , ErbB 2 , ErbB 3 , and ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
An overexpression of sox 2 , sox 10 , pax 6 , fzd , erbB 2 , and erbB 4 is found in nestin positive MSCs . ^^^
Interacting proteins: Q15303 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 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Here , we demonstrate that NMJs can form in the absence of the NRG receptors ErbB 2 and ErbB 4 in mouse muscle . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
ErbB 1 and erbB 4 do not compensate for the loss of erbB 2 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
EGFR : HER 2 or HER 4 : HER 2 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Furthermore , heregulin fails to induce phosphorylation of HER 2 in the absence of HER 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
HB EGF binds to NIH 3T3 cells overexpressing either HER 1 or HER 4 alone , but not HER 2 or HER 3 alone . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
In cells coexpressing HER 2 and HER 4 , however , both kinases significantly contribute to the HRG induced mitogenic stimulus . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
HER 1 , HER 2 , HER 3 and HER 4 ) in the cell lines employed and correlated this to their respective heregulin responses . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The primary cell surface targets of heregulins are heterodimers of the EGF receptor homolog HER 2 with either HER 3 or HER 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
HB 2 cells were found to express the heregulin receptor subunits HER 2 and HER 3 , but not HER 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
HER 1 , HER 2 , HER 3 , and HER 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The co receptor for HER 3 and HER 4 is HER 2 / neu , which is also present in epidermal cells but not overexpressed . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
In such tumors , HER 2 functions as a preferred coreceptor to form heterodimers with HER 1 ( EGFR ) , HER 3 or HER 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The relative levels of HER 2 , EGFR , HER 3 and HER 4 were not predictive of responsiveness to mAb 4D5 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Immunohistochemistry using epidermal growth factor receptor , HER 2 , HER 3 , HER 4 , and PR antibodies was done . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
All primary tumors examined expressed readily detectable levels of HER 1 and HER 3 and lower levels of HER 2 and HER 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Binding and cross linking experiments demonstrated that p 45 specifically binds to cells expressing recombinant p180erbB4 and not cells expressing recombinant p185erbB2 . . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Neuregulin can bind directly to erbB 3 and erbB 4 and receptor heterodimerization allows neuregulin dependent activation of erbB 2 ( refs 1 , 2 , 5 ) . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The family currently consists of four closely related members : the epidermal growth factor receptor ( EGF R / erbB 1 ) , erbB 2 , erbB 3 and erbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Studies of mRNA from CWR 22 have demonstrated the expression of prostate specific antigen and the epidermal growth factor receptor family including erbB1 / epidermal growth factor receptor , erbB2 / neu , and erbB 3 , but not erbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
However , the levels of erbB 2 mRNA were similar in both cell types , while the expression of erbB 4 mRNA was upregulated in the neoplastic fibroblasts . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Ecotropic virus , which normally does not infect human cells , when pseudotyped with the modified envelope protein now crosses species to infect human breast cancer cell lines that overexpress HER 2 ( human epidermal growth factor receptor ; also called ERBB 2 ) and HER 4 ( also called ERBB 4 ) , while human breast cancer cell lines expressing low levels of these receptors remain resistant to infection . ^^^
Interacting proteins: Q15303 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 . ^^^ The family of Neu differentiation factors ( NDFs , or heregulins ) includes a dozen secreted glycoproteins , whose receptor binding domain displays two variants , alpha and beta , and they bind to two receptor tyrosine kinases , ErbB 3 and ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
We show that C 2 muscle cells contain erbB 2 and erbB 3 messenger RNA but little or no erbB 4 mRNA , and that neuregulin stimulates tyrosine phosphorylation of erbB 2 and erbB 3 , indicating that neuregulin signalling in skeletal muscle may be mediated by a complex of erbB 2 and erbB3 . . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Recently a family of proteins known as heregulins ( HRGs ) has been isolated , characterized , and shown to interact with a number of class 1 receptor tyrosine kinases , including the erbB 2 , erbB 3 , and erbB 4 gene products . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
To address this question we constructed soluble chimeric proteins between alkaline phosphatase and the extracellular domains of ErbB 2 and either ErbB 3 or ErbB 4 , two newly recognized members of the epidermal growth factor receptor family . ^^^ Using the soluble proteins we found that beta isoforms of NDF specifically bind to the ErbB 3 and ErbB 4 receptors but not to the soluble ErbB 2 protein . ^^^ These results indicate that both ErbB 3 and ErbB 4 function as physiological receptors of all NDF isoforms and suggest that a still unknown ligand of ErbB 2 exists . . ^^^ ErbB 3 and ErbB 4 function as the respective low and high affinity receptors of all Neu differentiation factor / heregulin isoforms . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Neu differentiation factor activation of ErbB 3 and ErbB 4 is cell specific and displays a differential requirement for ErbB 2 . ^^^ Blocking cell surface expression of ErbB 2 by intracellular expression of a single chain antibody revealed that in these two cell lines , ErbB 2 significantly enhanced phosphorylation of ErbB 4 . ^^^ Neu differentiation factor activation of ErbB 3 and ErbB 4 is cell specific and displays a differential requirement for ErbB 2 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Four transmembrane tyrosine kinases constitute the ErbB receptor family : the epidermal growth factor ( EGF ) receptor , ErbB 2 , ErbB 3 , and ErbB 4 . ^^^
Interacting proteins: Q15303 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 . ^^^
Interacting proteins: Q15303 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 . ^^^
Interacting proteins: Q15303 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 . ^^^ 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 . . ^^^
Interacting proteins: Q15303 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 . ^^^ Two of these receptors , ErbB 3 and ErbB 4 , are known to bind a family of related proteins termed heregulins ( HRGs ) or neu differentiation factors . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Heregulins ( neuregulins ) are a family of proteins known to interact and activate the receptor tyrosine kinases ErbB 2 in association with ErbB 3 or ErbB 4 . ^^^
Interacting proteins: Q15303 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 ) . ^^^
Interacting proteins: Q15303 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 ) . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The epidermal growth factor receptor couples transforming growth factor alpha , heparin binding epidermal growth factor like factor , and amphiregulin to Neu , ErbB 3 , and ErbB 4 . ^^^
Interacting proteins: Q15303 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 . ^^^ In addition , the neu differentiation factor / heregulins ( HRGs ) , a family of ligands that activate p185erbB 2 through direct binding to erbB 3 or erbB 4 , are potent mitogens for various nonneoplastic mammary epithelial cells and carcinoma cell lines in the absence of both IGF and EGF in culture . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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: Q15303 and P04626	Pubmed	SVM Score :0.0
Whereas ErbB 1 binds to the epidermal growth factor ( EGF ) , both ErbB 3 and ErbB 4 bind to the Neu differentiation factors ( NDFs , or neuregulins ) , and ErbB 2 , the most oncogenic family member , is an orphan receptor whose function is still unknown . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
In this study , the effects of a putative erbB / HER ligand , gp 30 , on estrogen receptor ( ER ) concentration and activity was investigated in the estrogen receptor positive human breast cancer cells , BT 474 and MCF 7 , which express either high or low levels of erbB 2 and erbB 4 , respectively . ^^^ The effects of gp 30 on estrogen receptor concentration and activity were independent of the level of erbB 2 and erbB 4 in the cell . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Membrane proteins are solubilized via Triton 10 100 lysis and the receptor is captured in ELISA wells coated with ErbB 2 specific antibodies with no cross reaction to ErbB 3 or ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
In vitro studies on erbB 2 overexpressing cells have found a strong correlation between this oncogene overexpression and relative resistance to lymphokine activated killer ( LAK ) cell lysis . gp30 / heregulin / NDF ( neu differentiation factor ) , indirect activators of erbB 2 , are able to induce a more differentiated phenotype on erbB 2 overexpressing , erbB 3 and / or erbB 4 positive breast cancer cells . ^^^ In contrast we did not observe any enhancement of lysis of MCF 7 , a cell line that does not overexpress erbB 2 and is positive for the erbB 3 and erbB 4 receptors , after treatment with heregulin . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The dual label RP method should be useful for measuring the mRNA expression for other erbB 2 homologs such as erbB 3 and erbB 4 in tumor cells and tissues and can be a generally useful mRNA quantitative method for laboratories wishing to minimize radioisotope use . . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Recently , three studies have explored the in vivo function of the neuregulin signaling system in mice by disrupting the genes encoding the neuregulin ligand ( 1 ) and two of its receptors , ErbB 2 ( 2 ) and ErbB 4 ( 3 ) . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
EGF R , ErbB 3 , and ErbB 4 were not detected in the CHK immunoprecipitates or in the precipitates of the GST SH 2 fusion proteins of CHK , suggesting that the association of CHK with ErbB 2 upon heregulin stimulation is receptor specific ( ErbB 2 ) and ligand specific ( heregulin ) . ^^^
Interacting proteins: Q15303 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 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The heregulins ( HRGs ) are a family of growth factors that bind direction to erbB 3 and erbB 4 and induce tyrosine phosphorylation of erbB 2 via receptor heterodimerization . ^^^ 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 . ^^^ However , GRb 2 was detected in erbB 2 and erbB 4 but not erbB 3 immunoprecipitates . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The EGF family includes EGF , transforming growth factor alpha , heparin binding EGF , amphiregulin , beta cellulin , epiregulin , and heregulins , whereas the receptor family ( the erbB genes ) consists of erbB 1 ( EGF receptor , EGF R ) , erbB 2 , erbB 3 , and erbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Three signal transducing transmembrane receptors for neuregulins , which bear significant homology to the EGF receptor , are currently known : HER 2 ( erbB 2 ) , HER 3 ( erbB 3 ) , and HER 4 ( erbB 4 ) . ^^^
Interacting proteins: Q15303 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 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Through their interaction with the ErbB family of receptors ( ErbB 2 , ErbB 3 and ErbB 4 ) , neuregulins help to regulate cell growth and differentiation in many tissues . ^^^ Recombinant neuregulin 2beta induces the tyrosine phosphorylation of ErbB 2 , ErbB 3 and ErbB 4 in cell lines expressing all of these ErbB family receptors . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
We have isolated four splice variants , two each from human and mouse , and have shown that they are capable of inducing tyrosine phosphorylation of erbB 3 , erbB 4 , and erbB 2 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The class 1 tyrosine kinase growth factor receptors include epidermal growth factor receptor ( EGFR ) , ErbB 2 ( c erbB 2 , HER 2 / neu ) , ErbB 3 and ErbB 4 . ^^^ EGFR was expressed in the basal cells of normal urothelium , while ErbB 2 , ErbB 3 and ErbB 4 were present mainly in the superficial layer . ^^^ Both BCL 2 protein and Ki 67 antigen ( MIB 1 ) showed a strong positive association with EGFR ( P = 0 . 002 ) and an inverse correlation with ErbB 2 , ErbB 3 or ErbB 4 ( P = 0 . 0004 , 0 . 0000 , and 0 . 001 , respectively ) . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Schwann cells associated with these mechanoreceptors are immunoreactive for the neuregulin receptors erbB 2 , erbB 3 , and erbB 4 , and the sensory nerve terminals are immunoreactive for neuregulin . ^^^
Interacting proteins: Q15303 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 . ^^^ 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 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Heregulins bind directly to ErbB 3 and ErbB 4 receptors , leading to multiple dimerization possibilities including heterodimerization with the ErbB 2 receptor . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Consistent with these effects of neuregulin , we find that granule cells express its receptors ErbB 2 and ErbB 4 before the NR2C subunit of the NMDA receptor . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Two receptor tyrosine kinases , ErB 3 and ErbB 4 , mediate signaling by Neu differentiation factors ( NDFs , also called neuregulins ) , while ErbB 1 and ErbB 2 serve as co receptors . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Epiregulin binds to epidermal growth factor receptor and ErbB 4 and induces tyrosine phosphorylation of epidermal growth factor receptor , ErbB 2 , ErbB 3 and ErbB 4 . ^^^ Chemical cross linking experiments showed that [ 125I ] epiregulin directly bound to each of EGFR and ErbB 4 but not to ErbB 2 and ErbB 3 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Activation of ErbB 2 by neuregulins occurs in heterodimeric complexes with ErbB 3 and ErbB 4 . ^^^ A panel of human glioma cell lines , which had previously been analyzed for ErbB 2 expression , was examined for ErbB 3 and ErbB 4 expression . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The type 1 family of growth factor receptors consists of the epidermal growth factor receptor ( EGFR ) , and ErbB 2 , ErbB 3 and ErbB 4 . ^^^ Six ligands are known to bind directly to EGFR , none ( at present ) to ErbB 2 , and a family of ligands collectively called the neuregulins bind to both ErbB 3 and ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
This , along with the detection of elevated erbB 2 or erbB 4 specific transcripts in most ( six of eight ) neoplastic cell lines tested , supports the notion that autocrine neuregulin signaling plays an important role in maintaining the transformed phenotype by providing a growth advantage to cph transformed cells . . ^^^ 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: Q15303 and P04626	Pubmed	SVM Score :0.0
Two homologous epithelial receptors , ErbB 3 and ErbB 4 , bind all isoforms of another family of growth factors , the Neu differentiation factors ( NDFs / neuregulins ) . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Persistence of ErbB 2 and ErbB 4 expression in neonatal and adult ventricular myocytes . ^^^ 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 . ^^^ Both ErbB 2 and ErbB 4 receptors were found to be expressed by neonatal and adult ventricular myocytes and activated by rhGGF 2 . rhGGF 2 ( 30 ng / ml ) provoked an approximate 2 fold increase in embryonic cardiac myocyte proliferation . rhGGF 2 also promoted survival and inhibited apoptosis of subconfluent , serum deprived myocyte primary cultures and also induced hypertrophic growth in both neonatal and adult ventricular myocytes , which was accompanied by enhanced expression of prepro atrial natriuretic factor and skeletal alpha actin . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Activation of ErbB 4 by the bifunctional epidermal growth factor family hormone epiregulin is regulated by ErbB 2 . ^^^ Finally , ErbB 2 , which is not activated by EPR when expressed on its own , increases the sensitivity of ErbB 4 for activation by EPR . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The erbB 2 proto oncogene belongs to a receptor tyrosine kinase family that includes the epidermal growth factor receptor , erbB 2 , erbB 3 , and erbB 4 . erbB 2 is expressed in basal cells of the squamous epithelia and the outer root sheath of the hair follicles , but its function in epidermal development has not been well studied . ^^^
Interacting proteins: Q15303 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 . ^^^ 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: Q15303 and P04626	Pubmed	SVM Score :0.0
All of the mutants tested were able to induce phosphorylation and mitogen activated protein kinase activation through ErbB 4 receptors and were able to modulate a transphosphorylation signal from ErbB 3 to ErbB 2 in MCF 7 cells . ^^^
Interacting proteins: Q15303 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: Q15303 and P04626	Pubmed	SVM Score :0.0
Ten of 12 tumors expressed erbB 4 at moderate to high levels in > 50 % of cancer cells , whereas erbB 2 ( 6 of 12 ) and erbB 3 ( 2 of 12 ) were expressed less frequently . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
METHODS : A total of 17 serous cystadenocarcinomas were analyzed for epidermal growth factor receptor ( EGF R or ErbB 1 ) and ErbB 2 , ErbB 3 , and ErbB 4 receptor expression by Western blot analysis . ^^^ RESULTS : All 17 tumors expressed detectable levels of EGF R , ErbB 2 , and ErbB 3 , but ErbB 4 expression was not detected . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
ErbB 2 expression increases the spectrum and potency of ligand mediated signal transduction through ErbB 4 . ^^^ Although coexpression of ErbB 2 with ErbB 4 in 32D . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The ErbB family of receptors , which include the epidermal growth factor receptor ( EGFR ) , ErbB 2 , ErbB 3 , and ErbB 4 mediate the actions of a family of bioactive polypeptides . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
In order to identify whether EGF like growth factors and corresponding receptors ( erbB 2 , erbB 3 , and erbB 4 ) could be involved in the autonomous growth of these transformed rat thyroid epithelial cells , Northern blot for mRNA analysis and Western blot for protein expression were performed . ^^^ These data indicate that unlike the erbB 2 overexpressing FRTL 5 cells , in K ras rat thyroid epithelial cells , the growth factor heregulin signals through the heterodimer erbB 2 / erbB 4 receptors in an autocrine fashion . . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
When this protein was immunoprecipitated with antibody against epidermal growth factor receptors ErbB 1 , ErbB 2 , ErbB 3 or ErbB 4 , it was immunoprecipitated only by the anti ErbB 1 antibody . ^^^ Betacellulin induced the tyrosine phosphorylation of ErbB 1 , ErbB 2 and ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Expression of receptors for neuregulins , ErbB 2 , ErbB 3 and ErbB 4 , in developing mouse cerebellum . ^^^ We have examined the expression of ErbB 2 , ErbB 3 and ErbB 4 in developing mouse cerebellum . ^^^ ErbB 2 , ErbB 3 and ErbB 4 were all expressed in granule cells during cerebellar development . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Formation of a high affinity heregulin binding site using the soluble extracellular domains of ErbB 2 with ErbB 3 or ErbB 4 . ^^^ Heregulin binding analysis revealed that a heterodimer composed of either ErbB 3 or ErbB 4 with ErbB 2 is sufficient for the formation of a high affinity binding state . ^^^
Interacting proteins: Q15303 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: Q15303 and P04626	Pubmed	SVM Score :0.0
ErbB 3 is a transmembrane signaling molecule that shares close structural homology with epidermal growth factor receptor ( EGFR ) , erbB 2 , and erbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The four receptor tyrosine kinase 1 receptors , ErbB 1 , ErbB 2 , ErbB 3 , and ErbB 4 , which have been implicated in the development of a variety of normal and malignant tissues , are activated through ligand mediated homo and heterodimerization . ^^^ We have previously reported the frequent coexpression , heterodimerzation , and prognostic significance of ErbB 2 and ErbB 4 in childhood medulloblastoma , an embryonal tumor of the cerebellar external granule cell layer ( EGL ) . ^^^ Therefore , we propose that positive deregulation of ErbB 2 expression in the cerebellar EGL , leading to the formation of a NRG 41 beta driven ErbB 2 / ErbB 4 autocrine loop , is an important factor in medulloblastoma tumorigenesis . ^^^ In further support of this hypothesis , we provide evidence using reverse transcription PCR analysis that expression of the ErbB 2 and ErbB 4 receptors , but not ErbB 1 or ErbB 3 , is deregulated in medulloblastoma compared with normal developing cerebellum . ^^^ We also demonstrate NRG 1 beta expression in 87 % ( n = 46 of 48 ) of medulloblastoma primary tumors , with the greatest expression levels occurring in tumors with high ErbB 2 and ErbB 4 receptor coexpression . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
This suggests that the mutant EGF R signals through heterodimerization with endogenous , kinase active members of the EGF R family such as ErbB 2 or ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The p 185 ( c erbB 2 ) tyrosine kinase receptor can be activated with agonistic antibodies directed against p 185 ( c erbB 2 ) or with the ligand heregulin through a combinatorial interaction with erbB 3 or erbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Cytolysis of tumor cells expressing the Neu / erbB 2 , erbB 3 , and erbB 4 receptors by genetically targeted naive T lymphocytes . ^^^ Human heregulin beta 1 ( ligand to the erbB 3 and erbB 4 receptors ) and three different single chain antibodies specific for the human and rat Neu / erbB 2 receptors were used . ^^^ Target cells expressing Neu / erbB 2 , erbB 3 , or erbB 4 were lysed in vitro with high specificity by T cells expressing the corresponding recognition proteins . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The human epidermal growth factor receptor ( HER or ErbB ) family consists of four distinct members , including the epidermal growth factor ( EGF ) receptor ( EGFR , HER 1 , or ErbB 1 ) , ErbB 2 ( HER 2 or neu ) , ErbB 3 ( HER 3 ) , and ErbB 4 ( HER 4 ) . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Amplification of erbB 4 oncogene occurs less frequently than that of erbB 2 in primary human breast cancer . ^^^ We therefore used the double differential polymerase chain reaction ( ddPCR ) for determination of the amplification profile of erbB 4 and erbB 2 , another gene from the ErbB family , in human primary breast cancer specimens . ^^^ Amplification of erbB 2 was detected in 19 % and erbB 4 in 13 % of the samples studied . ^^^ Human breast cancer derived cell lines in most cases overexpress both erbB 2 and erbB 4 ( Beerli et al . , 1995 . ^^^ USA 92 , 9747 9751 ) , but data on separate erbB 2 overexpression , without overexpression of erbB 4 , were also reported ( Wosikowski et al . , 1997 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The epidermal growth factor ( EGF ) receptor ( EGFR ) family includes four homologous transmembrane receptor protein tyrosine kinases , EGFR , ErbB 2 , ErbB 3 , and ErbB 4 . ^^^ Betacellulin , a ligand for EGFR , ErbB 3 , and ErbB 4 , induced DNA synthesis of HASM cells and stimulated signaling through the activation of EGFR and ErbB 2 but not of ErbB 3 and ErbB 4 . ^^^ Despite the mRNA and protein expression of all members of the EGFR family , ligand stimulated signaling induced activation of EGFR and ErbB 2 but not of ErbB 3 and ErbB 4 . . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The erbB 4 gene encodes a detected receptor protein that possesses intrinsic tyrosine kinase activity and belongs to the family of the epidermal growth factor receptor ( EGFR ) ; erbB 4 is stimulated by the heregulins and betacellulin , which enables this receptor to form heterodimers with erbB 2 , a prerequisite for erbB 2 activation . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Overall , serum positivity was most frequently directed against ErbB 2 followed by EGFR , ErbB 3 and ErbB 4 . ^^^ Specificity patterns comprised tumor patients with unique serum reactivity against ErbB 2 or ErbB 4 . ^^^ Moreover , approximately half of the positive sera exhibited concomitant reactivity with multiple ErbB receptors including EGFR and ErbB 2 , EGFR and ErbB 4 , ErbB 2 and ErbB 3 or EGFR , ErbB 2 and ErbB 3 . ^^^ These findings implicate multiple ErbB receptors including ErbB 3 and ErbB 4 in addition to EGFR and ErbB 2 in primary human cancer . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Neu differentiation factors ( NDFs ) , or neuregulins , are epidermal growth factor like growth factors which bind to two tyrosine kinase receptors , ErbB 3 and ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
AIM : The type 1 family of growth factor receptors includes ErbB 1 , ErbB 2 , ErbB 3 , and ErbB 4 which are frequently overexpressed in various human cancer cells . ^^^
Interacting proteins: Q15303 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 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
These studies also revealed that ErbB 2 preferentially enhances ligand binding to ErbB 3 or ErbB 4 and to a lesser degree to ErbB1 . . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The receptors erbB 3 and erbB 4 are members of the type 1 tyrosine kinase receptor family which also comprises epidermal growth factor receptor ( EGF R ) and erbB 2 . ^^^ Immunoprecipitation , using antibodies to erbB 2 , erbB 3 or erbB 4 receptors , coupled to phosphotyrosine Western blot analysis indicates that these three receptors are constitutively tyrosine phosphorylated in lung cancer cell lines , but only erbB 2 and erbB 3 are autophosphorylated in normal cells . ^^^ These data suggest that constitutive activation of erbB 2 , erbB 3 and erbB 4 receptors could be induced by heregulin alpha via an autocrine loop mechanism , and that the active forms of erbB 4 may cooperate with the other members of the EGF receptor family in human lung carcinogenesis . . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
In this report we show that ErbB 2 , ErbB 3 , and ErbB 4 do not potentiate Stat 5 phosphorylation by EGF . ^^^ However , neu differentiation factor induced heterodimers of ErbB 2 and ErbB 4 activated Stat 5 . ^^^
Interacting proteins: Q15303 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 . ^^^ Neu differentiation factor ( NDF ) / heregulin activates ErbB 2 via heterodimerization with the NDF receptors ErbB 3 and ErbB 4 . ^^^
Interacting proteins: Q15303 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: Q15303 and P04626	Pubmed	SVM Score :0.0
Differential expression of erbB 2 and erbB 4 receptors . ^^^ METHODS AND RESULTS : We used ribonuclease protection assays to quantify mRNA levels of neuregulin , erbB 2 , and erbB 4 in left ventricular ( LV ) tissue and myocytes of normal rats and rats with aortic stenosis with pressure overload hypertrophy 6 and 22 weeks after banding . ^^^ LV erbB 2 and erbB 4 message levels in LV tissue and myocytes were maintained during early compensatory hypertrophy in 6 week aortic stenosis animals compared with age matched controls ; in contrast , erbB 2 and erbB 4 message levels were depressed in 22 week aortic stenosis animals at the stage of early failure ( both P < 0 . 01 vs age matched controls ) . ^^^ Immunoblotting of erbB 2 and erbB 4 also showed normal protein levels in 6 week aortic stenosis animals compared with controls ; however , erbB 2 and erbB 4 protein levels were depressed in 22 week aortic stenosis animals ( 48 % decrease in erbB 2 , P < 0 . 05 , and 43 % decrease in erbB 4 , P < 0 . 01 ) relative to age matched controls . ^^^ CONCLUSIONS : The neuregulin receptors erbB 2 and erbB 4 are downregulated at both the message and protein levels at the stage of early failure in animals with chronic hypertrophy secondary to aortic stenosis . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The family has three other receptors erbB 2 , erbB 3 , and erbB 4 , which have their own ligands ( the heregulins ) . ^^^ The heart of the minipigs was also enlarged , an interesting finding regarding interactions between the different parts of the EGF system , as knock out mice of the receptors erbB 2 and erbB 4 die due to maldevelopments in the heart . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
They stimulate LHRH secretion indirectly , via activation of erbB 1 / erbB 2 and erbB 4 / erbB 2 receptor complexes also located on astrocytes . ^^^ They ( a ) increase astrocytic gene expression of at least one of the EGF related ligands ( TGFalpha ) , ( b ) increase expression of at least two of the receptors ( erbB 4 and erbB 2 ) , and ( c ) enhance the LHRH response to PGE ( 2 ) by up regulating in LHRH neurons the expression of specific PGE ( 2 ) receptor isoforms . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The ErbB 2 tyrosine kinase functions as coreceptor for the neuregulin receptors ErbB 3 and ErbB 4 and can participate in signaling of EGF receptor ( ErbB 1 ) , interleukin receptor gp 130 , and G protein coupled receptors . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
RESULTS : Cancer cell lines and rat epithelial cells expressed erbB 2 and erbB 3 , but protein expression of erbB 4 was not detected . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
No effects were observed in estrogen receptor negative ( ER ) MDA MB 453 cells , which express low levels of endogenous ErbB 4 and high levels of ErbB 2 and ErbB 3 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Neuregulins signaling via a glial erbB 2 erbB 4 receptor complex contribute to the neuroendocrine control of mammalian sexual development . ^^^ Here , we show that activation of astrocytic erbB 2 / erbB 4 receptors plays a significant role in the process by which the hypothalamus controls the advent of mammalian sexual maturation . ^^^ Hypothalamic astrocytes express both the erbB 2 and erbB 4 genes , but no erbB 3 , and respond to neuregulins ( NRGs ) by releasing prostaglandin E ( 2 ) ( PGE ( 2 ) ) , which acts on neurosecretory neurons to stimulate secretion of luteinizing hormone releasing hormone ( LHRH ) , the neuropeptide controlling sexual development . ^^^ The actions of TGFalpha and NRGs in glia are synergistic and involve recruitment of erbB 2 as a coreceptor , via erbB 1 and erbB 4 , respectively . ^^^ Hypothalamic expression of both erbB 2 and erbB 4 increases first in a gonad independent manner before the onset of puberty , and then , at the time of puberty , in a sex steroid dependent manner . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Targeted disruption of neuregulin ( NRG ) 1 or one of two of its cognate receptors , ErbB 2 or ErbB 4 , results in embryonic lethality because of failure of the heart to develop . ^^^ 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: Q15303 and P04626	Pubmed	SVM Score :0.0
However the kinase activity of erbB 2 can be activated without any ligand , if it is overexpressed , and by heteroassociation with other members of the erbB family ( erbB 1 or epidermal growth factor receptor , erbB 3 and erbB 4 ) . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Changes in ErbB 2 ( her 2 / neu ) , ErbB 3 , and ErbB 4 during growth , differentiation , and apoptosis of normal rat mammary epithelial cells . ^^^ Studies were undertaken to examine the natural role of ErbB 2 , ErbB 3 , and ErbB 4 during the development of normal rat mammary epithelial cells ( MECs ) in vivo and in vitro . ^^^ Immunohistochemical analysis demonstrated that mammary gland terminal end buds expressed abundant ErbB 2 and ErbB 4 but limited ErbB 3 in pubescent rats , whereas luminal epithelial cells in nulliparous rats expressed ErbB 2 , ErbB 3 , and / or ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Expression of the EGF receptor family members ErbB 2 , ErbB 3 , and ErbB 4 in germinal zones of the developing brain and in neurosphere cultures containing CNS stem cells . ^^^ The epidermal growth factor receptor family consists of four related tyrosine kinases : the epidermal growth factor receptor ( EGF R or ErbB ) , ErbB 2 , ErbB 3 , and ErbB 4 . ^^^ Since EGF R is expressed by proliferating cells in the central nervous system ( CNS ) , including multipotent CNS stem cells , we examined the expression of ErbB 2 , ErbB 3 and ErbB 4 in the germinal epithelia of the developing rat brain using in situ hybridization . ^^^ ErbB 2 and ErbB 4 mRNAs were widely distributed within the germinal zones as early as E 12 . ^^^ However , as development proceeded , ErbB 2 mRNA was mainly present within the layers of cells immediately adjacent to the ventricular surface the ventricular zone , while ErbB 4 mRNA was predominantly expressed by subventricular zone cells , in the regions where these specialized germinal epithelia were present . ^^^
Interacting proteins: Q15303 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 . ^^^ In human lymph node tissue , some lymphocytes were positive for erbB 2 , erbB 3 and erbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Immunohistochemical analyses of p 53 , epidermal growth factor receptor , erbB 2 , erbB 3 , erbB 4 , and Bcl 2 expression were performed . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
These studies demonstrate significant expression of the ErbB 2 , ErbB 3 , and ErbB 4 receptors , in addition to heregulin isoforms , in the developing murine fetal pancreas . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Neural and thymus derived activator for ErbB kinases ( NTAK ) is a recently described member of the neuregulin family that binds directly to ErbB 3 and ErbB 4 and transactivates ErbB 2 . ^^^ Although both NTAKs induce the highest level of tyrosine phosphorylation of ErbB 2 , NTAKalpha2a and NTAKbeta preferentially induce ErbB 3 and ErbB 4 phosphorylation , respectively . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The ErbB receptor tyrosine kinase family consists of the epidermal growth factor ( EGF ) receptor ( ErbB 1 ) and three related receptors ( ErbB 2 , ErbB 3 , ErbB 4 ) . ^^^ Overexpression of ErbB 1 , ErbB 2 and ErbB 4 receptors was enough to activate them as judged by their phosphorylation , whereas co expression of other ErbB receptors was necessary for the phosphorylation of the ErbB 3 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The neu differentiation factors / heregulins ( HRGs ) comprise a family of polypeptide growth factors that activate p 185 ( erbB 2 ) through direct binding to either erbB 3 or erbB 4 receptor tyrosine kinases . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Neuregulins signal cells by binding to an activating hetero and homodimeric forms of the neuregulin receptors HER 2 ( erbB 2 ) , HER 3 ( erbB 3 ) , and HER 4 ( erbB 4 ) . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
A new ligand ( ASGP 2 ) for ErbB 2 has been discovered which operates by an intramembrane mechanism and may be able to modulate external ligand dependent ErbB 3 or ErbB 4 heterodimeric interactions with ErbB 2 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
ErbB 2 is a member of the ErbB / type 1 family of receptor tyrosine kinases which also includes epidermal growth factor receptor , ErbB 3 and ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
TaqMan quantitative RT PCR analysis and immunocytochemistry reveal that heregulin and its binding receptors ( ErbB 2 , ErbB 3 and ErbB 4 ) are expressed in the inner ear sensory epithelium . ^^^ Because neuregulin 3 that signals only through ErbB 4 does not show an effect , these data suggest that activation of the ErbB 2 ErbB 3 heterodimeric complexes , rather than ErbB 4 , is critical for the proliferative response in the utricular sensory epithelium . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Unique carboxyl terminal sequences of wild type and alternatively spliced variant forms of transforming growth factor alpha precursors mediate specific interactions with ErbB 4 and ErbB 2 . ^^^ WT co immunoprecipitated with ErbB 4 , but not with ErbB 1 , ErbB 2 , or ErbB 3 . ^^^ VaI and VaII co immunoprecipitated with ErbB 2 , but not with ErbB 1 , ErbB 3 , or ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
We report the effect of heregulin beta 1 , the ligand for erbB 3 and erbB 4 receptors , on the regulation of vascular endothelial growth factor ( VEGF ) expression , using a panel of breast and lung cancer cell lines with constitutive erbB 2 overexpression or engineered to stably overexpress the erbB 2 receptor . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
These decorin mediated effects appear to involve the activation of ErbB 4 , which in turn would block the phosphorylation of heterodimers containing either ErbB 2 or ErbB 3 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The erbB family of receptor tyrosine kinases , which consists of the epidermal growth factor receptor ( EGFr / erbB1 ) , erbB 2 ( neu ) , erbB 3 and erbB 4 , has been shown to be important for both normal development as well as neoplasia . ^^^
Interacting proteins: Q15303 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 . ^^^ The erbB 3 and erbB 4 receptors are involved in transregulation of erbB 2 signaling . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Heregulin binds erbB receptors , and in our studies , primary cultures of both oligodendrocyte progenitor cells and differentiating oligodendrocytes expressed erbB 2 , erbB 3 , and erbB 4 receptors . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Estrogen and progesterone facilitate erbB mediated glia to LHRH neuron communication by enhancing astrocytic gene expression of at least one of the EGF related ligands ( TGFalpha ) and two of the receptors ( erbB 2 and erbB 4 ) . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Ethanol increased erbB 2 , erbB 3 , and erbB 4 expression in T47D human breast cancer cells in a concentration dependent manner . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
ErbB 4 receptor tyrosine kinase and its ligand neu differentiation factor ( NDF / neuregulin ) are widely expressed in the brain . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
ErbB 2 , erbB 3 , and erbB 4 as well as neuregulin , agrin , and MuSK are known to be concentrated at the NMJ . ^^^ We have determined that erbB 2 and erbB 4 are enriched in the depths of the secondary junctional folds on the postsynaptic muscle membrane . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Our recent studies indicate that ErbB 4 interacts with postsynaptic density ( PSD ) 95 ( SAP 90 ) , a PDZ domain containing protein that does not interact with ErbB 2 or ErbB 3 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The ErbB family of receptors , which includes the epidermal growth factor receptor ( EGFR ) , ErbB 2 , ErbB 3 , and ErbB 4 , mediate signaling by EGF like polypeptides . ^^^ K721M alone exhibited no detectable signaling capacity , whereas coexpression of K721M with ErbB 2 , but not ErbB 3 or ErbB 4 , resulted in EGF dependent mitogen activated protein kinase ( MAPK ) activation . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Tumors of serous histology were more likely to express a higher level of erbB 4 than endometrioid tumors , and for stage 3 serous tumors , long term survival was associated with moderate to high coexpression of erbB 4 and erbB 2 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The present study showed that erbB 2 , erbB 3 , and erbB 4 transcripts and protein are distributed throughout all areas of adult rat brain . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Previously , we documented the expression of type 1 growth factor receptors [ ERBB1 / EGFR ( epidermal growth factor receptor ) , ERBB 2 , ERBB 3 and ERBB 4 ] in the full range of cervical neoplasias by immunohistochemistry assay . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
A naturally occurring secreted human ErbB 3 receptor isoform inhibits heregulin stimulated activation of ErbB 2 , ErbB 3 , and ErbB 4 . ^^^ 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 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
We show here that embryonic striatal NPs express multiple Nrg 1 transcripts and proteins as well as their specific receptors , ErbB 2 and ErbB 4 , but not ErbB 3 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Expression of individual EGF receptor ( EGFR ) and ErbB 2 , ErbB 3 , or ErbB 4 receptors was detected in 72 . 2 , 44 . 5 , 56 . 3 , and 29 . 8 % of bladder cancer cases , respectively . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
In contrast , the phenotypes of transgenic mice expressing dominant negative ERBB 2 and ERBB 4 proteins suggest that these receptors differentially act to promote or maintain alveolar differentiation . ^^^
Interacting proteins: Q15303 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: Q15303 and P04626	Pubmed	SVM Score :0.0
Human skin , cultured normal keratinocytes , and A 431 skin carcinoma cells expressed ErbB 1 , ErbB 2 , and ErbB 3 , but not ErbB 4 . ^^^
Interacting proteins: Q15303 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 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Among invasive and in situ carcinoma , EGFR expression was the most prevalent ( in 29 / 32 and 8 / 11 cases , respectively ) followed by ErbB 2 ( 17 / 32 and 2 / 11 ) and ErbB 4 ( 9 / 32 and 1 / 10 ) , while ErbB 3 was only detected in invasive tumours ( 12 / 32 ) . ^^^ Some benign lesions and histologically normal mucosa adjacent to carcinomas showed weak immunostaining of EGFR ( 10 / 28 ) , ErbB 2 ( 4 / 28 ) or ErbB 4 ( 3 / 28 ) . ^^^ By comparison , overexpression , as indicated by increased staining intensity , was observed in invasive tumours for EGFR ( 18 / 32 ) , ErbB 2 ( 8 / 32 ) , ErbB 4 ( 3 / 32 ) , and ErbB 3 ( 3 / 32 ) . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Epidermal growth factor receptor ( EGFR ) , ErbB 2 , and ErbB 4 are members of the type 1 receptor tyrosine kinase family . ^^^ Here we describe the expression , purification , and biochemical comparison of EGFR , ErbB 2 , and ErbB 4 intracellular domains . ^^^ ErbB 2 uses ATP Mg as a substrate inefficiently compared with EGFR and ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
In addition , erbB 2 is thought to participate in an important pathway for growth , repair , and survival of adult cardiomyocytes as part of a signaling network that involves neuregulins and the neuregulin receptor erbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
This inhibition is highly selective for erbB 1 ( epidermal growth factor receptor ) , erbB 2 , erbB 3 , and erbB 4 without inhibiting tyrosine kinase activity of receptors such as platelet derived growth factor receptor , fibroblast growth factor receptor , and insulin receptor , even at high concentrations . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Activation of ErbB1 / EGFR is mainly triggered by epidermal growth factor ( EGF ) and other related ligands , while activation of ErbB 2 , ErbB 3 , and ErbB 4 receptors occurs by binding to another set of EGF like ligands termed neuregulins ( NRGs ) . ^^^ Analysis of Erk 5 in several human tumor cell lines indicated that a constitutively active form of this kinase was present in the BT 474 and SKBR 3 cell lines , which also expressed activated forms of ErbB 2 , ErbB 3 , and ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Specifically , ligand dependent ErbB 2 transactivation requires a discrete three amino acid segment , located at the C terminus of ErbB family members ErbB 3 , ErbB 4 , and the epidermal growth factor receptor . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Nrdp 1 interacts specifically with the neuregulin receptors ErbB 3 and ErbB 4 and not with epidermal growth factor receptor or ErbB 2 . ^^^ When coexpressed in COS 7 cells , Nrdp 1 mediates the redistribution of ErbB 3 from the cell surface to intracellular compartments and induces the suppression of ErbB 3 and ErbB 4 receptor levels but not epidermal growth factor receptor or ErbB 2 levels . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Particularly , the interactions among ErbB 1 and ErbB 2 or ErbB 4 and ErbB 2 are known to be involved in the stimulation of LHRH secretion during sexual maturation . ^^^ Disruption of functional ErbB 4 / 2 receptor complex by blocking ErbB 2 receptor synthesis in the hypothalamus via an infusion of ErbB 2 antisense oligodeoxynucleotide resulted in an estrous acyclicity in young adult rats . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Members of the erbB family receptor tyrosine kinases ( erbB 1 , erbB 2 , erbB 3 , and erbB 4 ) are overexpressed in a variety of human cancers and represent important targets for the structure based drug design . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
ErbB 2 and ErbB 3 do not quantitatively modulate ligand induced ErbB 4 tyrosine phosphorylation . ^^^ One expresses ErbB 4 alone , the second expresses ErbB 2 and ErbB 4 , and the third expresses ErbB 3 and ErbB 4 . ^^^ ErbB 2 and ErbB 3 do not affect the amount of ligand induced ErbB 4 tyrosine phosphorylation . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
In A 549 and H 322 cells , which express a detectable amount of EGF R ( ErbB 1 ) , ErbB 2 , ErbB 3 , and ErbB 4 receptors , the LA 1 mAb induces up regulation of the E cadherin / catenin complex ( alpha , beta , and gamma catenins ) . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Gene ablation studies have previously demonstrated that the ErbB 2 receptor , together with its coreceptor ErbB 4 and the ligand Neuregulin 1 , are essential for normal development of the heart ventricle . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Constitutively active ErbB 4 and ErbB 2 mutants exhibit distinct biological activities . ^^^ Unlike a constitutively active ErbB 2 mutant , the ErbB 4 mutants are not coupled to increased cell proliferation , loss of contact inhibition , or anchorage independence in a rodent fibroblast cell line . ^^^ This suggests that ErbB 2 and ErbB 4 may play distinct roles in tumorigenesis in vivo . . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The erbB receptor family is part of the receptor tyrosine kinase superfamily and consists of four members , erbB 1 , erbB 2 , erbB 3 , and erbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
ErbB 4 associates with the PSD 95 ( also known as SAP 90 ) family members including PSD 95 , SAP 97 , and SAP 102 whereas ErbB 2 interacts with Erbin and PICK 1 . ^^^
Interacting proteins: Q15303 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 . ^^^ HRGbeta 1 treatment of LM 3 cells induced tyrosine phosphorylation of ErbB 2 , ErbB 3 and ErbB 4 as well as the formation of ErbB 2 / ErbB 3 and ErbB 2 / ErbB 4 heterodimers . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The neu ( c erbB 2 , HER 2 ) proto oncogene encodes a receptor tyrosine kinase that is a member of an important growth factor receptor family which includes the epidermal growth factor receptor ( EGFR , ErbB 1 ) , ErbB 3 and ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
PURPOSE : This study was designed to investigate the biological and therapeutic significance of ERBB 1 , ERBB 2 , ERBB 3 , and ERBB 4 in childhood ependymoma . ^^^ RESULTS : Coexpression of ERBB 2 and ERBB 4 was identified in over 75 % of tumors . ^^^ An analysis of ERBB 2 and ERBB 4 expression , in association with Ki 67 LI and the degree of surgical resection , may provide an accurate tool for assessing disease risk in children with this disease . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
We found the mean AGCNs of the oncogenes equal 1 . 18 for erbB 1 [ amplification was found in 11 / 35 cases ( 31 % ) and deletion in 6 / 35 cases ( 17 % ) ] , 2 . 00 for erbB 2 [ amplification was found in 8 / 34 cases ( 24 % ) , no deletion was found ] , 1 . 36 for erbB 3 [ amplification was found in 4 / 36 cases ( 11 % ) and deletion in 1 / 36 cases ( 3 % ) ] , and 1 . 22 for erbB 4 [ amplification was found in 5 / 30 cases ( 17 % ) and deletion in 1 / 30 cases ( 3 % ) ] . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The neuregulin ( NRG ) / epidermal growth factor ( EGF ) family of growth factors consists of several ligands that specifically activate four erbB receptor tyrosine kinases , namely erbB 1 ( EGF R ) , erbB 2 ( neu ) , erbB 3 , and erbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
This study is the first to examine the role of all members of the ErbB tyrosine kinase receptors ( epidermal growth factor receptor [ EGFR ] , ErbB 2 , ErbB 3 , or ErbB 4 ) , expressed singly or as paired receptor combinations , in the regulation of angiogenesis both in vitro and in vivo . ^^^ Comparison of all receptor combinations reveals that EGFR / ErbB 2 and ErbB 2 / ErbB 3 heterodimers are the most potent inducers of vascular endothelial growth factor ( VEGF ) mRNA expression compared with EGFR / ErbB 3 , EGFR / ErbB 4 , ErbB 2 / ErbB 4 , and ErbB 3 / ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
PURPOSE : To show the presence and localization of type 1 growth factor receptors ( ErbB 2 , ErbB 3 and ErbB 4 ) in rat corneal and conjunctival epithelia and investigate the association of ErbB 2 with its intramembrane ligand Muc 4 . ^^^ RESULTS : Immunocytochemical staining demonstrated the presence of ErbB 2 , ErbB 3 and ErbB 4 growth factor receptors throughout the rat corneal and conjunctival epithelia . ^^^ CONCLUSIONS : The three type 1 growth factor receptors ( ErbB 2 , ErbB 3 and ErbB 4 ) are present in the rat corneal and conjunctival epithelia , and ErbB 2 is at least partly associated with Muc 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Mice harboring targeted mutations in neuregulin 1 and its receptors ( erbB 2 , erbB 3 , and erbB 4 ) have been invaluable tools for testing the roles of these genes in vivo as well as for identifying unexpected functions for this signaling system . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Using real time quantitative PCR assays , mRNA levels of ERalpha , ERbeta , epidermal growth factor receptor , ErbB 2 , ErbB 3 , ErbB 4 , ERRalpha , ERRbeta , and ERRgamma were determined in unselected primary breast tumors ( n = 38 ) and normal mammary epithelial cells enriched from reduction mammoplasties ( n = 9 ) . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
DN erbB 4 expression is most abundant in hypothalamic astrocytes , where it blocks the ligand dependent activation of glial erbB 4 and erbB 2 receptors , without affecting erbB 1 ( EGF ) receptor signaling . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Western blot and immunofluorescence confirmed the expression of multiple NRG isoforms and the ErbB 2 , ErbB 3 , and ErbB 4 receptors in adult skeletal muscle . ^^^ Thus two distinct modes of exercise activated processing of NRG with concomitant stimulation of ErbB 2 , ErbB 3 , and ErbB 4 signaling in vivo . ^^^
Interacting proteins: Q15303 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: Q15303 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 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
HER 2 ( also known as Neu , ErbB 2 ) is a member of the epidermal growth factor receptor ( EGFR ; also known as ErbB ) family of receptor tyrosine kinases , which in humans includes HER 1 ( EGFR , ERBB 1 ) , HER 2 , HER 3 ( ERBB 3 ) and HER 4 ( ERBB 4 ) . ^^^ HER 2 ( also known as Neu , ErbB 2 ) is a member of the epidermal growth factor receptor ( EGFR ; also known as ErbB ) family of receptor tyrosine kinases , which in humans includes HER 1 ( EGFR , ERBB 1 ) , HER 2 , HER 3 ( ERBB 3 ) and HER 4 ( ERBB 4 ) . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
ErbB 2 does not bind ligand , yet appears to be the major signaling partner for other ErbB receptors by forming heteromeric complexes with ErbB 1 , ErbB 3 , or ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
HB EGF induced tyrosine phosphorylation of ErbB 2 and ErbB 4 , and to a lesser degree , of EGFR in cardiac myocytes . ^^^ In addition , constitutive tyrosine phosphorylation of both ErbB 2 and ErbB 4 was significantly reduced in HB ( del / del ) hearts . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Human airway epithelia constitutively produce both a ligand , the growth factor heregulin , and its receptors erbB 2 , erbB 3 and erbB 4 ( refs 1 3 ) . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
RT PCR analysis revealed that the EGF receptors erbB 1 , erbB 2 , erbB 3 and erbB 4 were expressed at all stages of the spermatogenic wave , whereas differential expression was found in isolated Leydig , Sertoli and peritubular cells . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Expression of epidermal growth factor receptor ( EGFr ) , erbB 2 , and erbB 3 , but not erbB 4 , was detected throughout the epidermis , although labeling for erbB 2 and erbB 3 was accentuated in the upper spinous layers , and EGFr was more strongly labeled in basal cells . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The epidermal growth factor receptor ( EGFR ) and related family members ( ERBB 2 , ERBB 3 , and ERBB 4 ) previously have been shown to play pivotal roles in the development of female reproductive tissues , in blastocyst implantation , and in placental differentiation . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
ErbB receptors ( ErbB 1 / epidermal growth factor receptor , ErbB 2 , ErbB 3 , and ErbB 4 ) were stably overexpressed in a polyclonal cell population as single or paired combinations using murine and human breast cell models . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Coimmunoprecipitation experiments also indicated that Grb 7 and NIK could be simultaneously recruited into signaling complexes of all known EGF / heregulin receptors , including EGFR , ErbB 2 , ErbB 3 , and ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
ERBB gene expression varied widely , by more than 2 orders of magnitude for ERBB 1 and ERBB 3 , more than 3 orders for ERBB 2 and more than 4 orders for ERBB 4 . ^^^ Compared to normal breast tissue , ERBB 1 was underexpressed ( 82 . 3 % of tumors ) , ERBB 2 ( 16 . 9 % ) and ERBB 3 ( 46 . 2 % ) were overexpressed and ERBB 4 was both underexpressed ( 24 . 6 % ) and overexpressed ( 29 . 2 % ) . ^^^ Relapse free survival ( RFS ) was shorter among patients with ERBB 3 overexpressing tumors ( p=0 . 0092 ) and longer among those with ERBB 4 underexpressing tumors ( p=0 . 0085 ) relative to patients with normal expression of the respective genes ; in contrast , RFS was not significantly influenced by ERBB 1 or ERBB 2 mRNA status . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
When the m 80 ErbB 4 fragment is generated by cell treatment with heregulin or 12 O tetradecanoylphorbol 13 acetate , the fragment associates with intact ErbB 2 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
During development and in the adult , erbB 2 , erbB 3 , and erbB 4 are expressed in many tissues and as heterodimers ( B2 / B3 , B2 / B4 ) serve as receptors for neuregulins . ^^^ The general importance of neuregulin receptors for development is underlined by the observed embryonic ( erbB 2 , erbB 4 ) or perinatal ( erbB 3 ) lethality in mouse mutants . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Endothelial derived heparin binding EGF like growth factor ( HB EGF ) was shown to mediate this process by signaling via ErbB 1 and ErbB 2 receptors in SMCs . 1 ) Analysis of ErbB ligands demonstrated that primary ECs expressed only HB EGF and neuregulin 1 . 2 ) Primary SMCs expressed ErbB 1 and ErbB 2 , but not ErbB 3 or ErbB 4 . 3 ) Consistent with their known receptor specificities , recombinant HB EGF , but not neuregulin 1 , stimulated tyrosine phosphorylation of ErbB 1 and ErbB 2 and migration in SMCs . 4 ) Neutralization of HB EGF or inhibition of ErbB 1 or ErbB 2 blocked 70 90 % of the potential of ECs to stimulate SMC migration . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Identification of patients with transitional cell carcinoma of the bladder overexpressing ErbB 2 , ErbB 3 , or specific ErbB 4 isoforms : real time reverse transcription PCR analysis in estimation of ErbB receptor status from cancer patients . ^^^ Determination of cutoff expression levels indicated tumor specific overexpression of ErbB 2 , ErbB 3 , and specific ErbB 4 isoforms in a subset of TCC patients . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
We have found that neuregulin 1beta ( NRG 1beta ) is expressed in the cardiac microvascular endothelium , and promotes the growth and survival of cardiac myocytes in culture through the activation of erbB 2 and erbB 4 receptor tyrosine kinases . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The epidermal growth factor receptor ( EGFR ) gives name to a family of receptors formed by four members in mammals ( EGFR , ErbB 2 , ErbB 3 , and ErbB 4 ) . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
NTAK ( neural and thymus derived activator for ErbB kinases ) , also known as neuregulin 2 , is a member of the epidermal growth factor ( EGF ) family , which binds directly to ErbB 3 and ErbB 4 and transactivates ErbB 2 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The tyrosine kinase receptor erbB 2 , also known in humans as Her 2 , is a member of the epidermal growth factor receptor ( EGFR or erbB 1 ) family , which also includes erbB 3 and erbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
DATA SOURCES : Published articles identified through MEDLINE using search terms such as tyrosine kinase , erbB 1 , erbB 2 , erbB 3 , erbB 4 , epidermal growth factor receptors ( EGFR ) , and EGFR inhibitors . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Overexpression of ErbB 2 and ErbB 4 receptors in breast cancers may be accompanied by contrasting clinical outcomes . ^^^ Agonistic antibodies were employed to activate ErbB 2 and ErbB 4 in isolation from the other ErbBs in breast cancer cells . ^^^ Our results indicate that , in the same cell line , ErbB 2 and ErbB 4 activation influence gene transcription differentially . ^^^ These include ErbB 4 targets EPS15R , GATA 4 , and RAB 2 and ErbB 2 activated HRY / HES1 and PPAP2A . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
SK N MC cells expressed multiple NRG 1 proteins and mRNAs encoding several alpha and beta isoforms from the sensory and motor neuron derived factor NRG 1 subfamily as well as the NRG 1 receptor subunits erbB 2 , erbB 3 , and erbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Neuregulin can bind directly to erbB 3 and erbB 4 receptors and receptor heterodimerization allows neuregulin dependent activation of erbB 2 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
In meningiomas , quantitative real time RT PCR revealed expression of EGFR , ErbB 2 , and ErbB 4 mRNA in the majority of the tumors . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Neuregulin 2 stimulates AChR transcription in cultured myotubes expressing ErbB 4 , as well as ErbB 3 and ErbB 2 , but not in myotubes expressing only ErbB 3 and ErbB 2 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
ErbB family members , such as epidermal growth factor receptor 1 ( erbB 1 ) , erbB 2 , erbB 3 and erbB 4 , are widely distributed in organ tissues , and these receptors are suspected tumorigenesis factors . ^^^ Additional studies indicated a similar result in papillary carcinoma cells ; mRNAs of erbB 2 and erbB 3 were increased but erbB 4 mRNA was decreased , suggesting distorted erbB expression may be associated with tumorigenesis . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Here we tested whether the related human LRIG 1 ( also called Lig 1 ) protein can act as a negative regulator of EGF receptor and its relatives , ErbB 2 , ErbB 3 , and ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
To examine the role of ErbB 4 in neuron migration , we cloned and stably transfected each of the four ErbB 4 isoforms in ST14A cells ( a neural progenitor cell line derived from the striatum of embryonic day 14 rats ) endogenously expressing the other members of the ErbB family : ErbB 1 , ErbB 2 , and ErbB 3 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
In summary the results showed that ErbB 2 mRNA was downregulated in conventional ( clear cell ) RCC ; ErbB 3 mRNA levels were low and heterogeneous in both tumours and kidney cortex ; ErbB 4 mRNA and protein were strongly downregulated in conventional and papillary RCC . ^^^ Thus , ErbB 2 and ErbB 4 are not likely to be oncogenes in the majority of RCCs ; instead , the observed downregulations suggest that these receptors might function as tumour suppressors in RCC . . ^^^
Interacting proteins: Q15303 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 . ^^^ Virtually all DRG neurons are erbB 2 and erbB 3 immunoreactive , with erbB 4 also detectable in many neurons . ^^^ In spinal cord white matter , erbB 2 and erbB 4 antibodies produce dense punctate staining , whereas the erbB 3 antibody primarily labels glial cell bodies . ^^^ Spinal cord dorsal and ventral horn neurons , including alpha motor neurons , exhibit erbB 2 , erbB 3 , and erbB 4 immunoreactivity . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Alterations of chromosomes ( 3p , 5q , 9p ) , genes ( Rb , C myc , C mos , hTERT ) , proteins ( p 16 , p 53 , K ras , hnRNP A2 / B1 , MCM 2 , EGFR , erbB 2 , erbB 3 , erbB 4 ) and others can be found in lung cancer . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
In an effort to elucidate the role of ErbB receptors in human head and neck squamous cell carcinoma ( HNSCC ) , expression abnormalities and subcellular localization of epidermal growth factor receptor ( EGFR ) , ErbB 2 , ErbB 3 , and ErbB 4 were investigated along with EGF and tenascin by immunohistochemistry in 38 carcinomas as compared to adjacent normal mucosa of 24 cases . ^^^ Although tumour specific overexpression affected each ErbB receptor ( EGFR 47 % , ErbB 2 29 % , ErbB 3 21 % , ErbB 4 26 % ) , EGFR abnormalities were most prevalent . ^^^
Interacting proteins: Q15303 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 . ^^^ We conclude that NRG 1beta stimulates hippocampal neurite extension and arborization via a signaling pathway that involves erbB membrane tyrosine kinases ( erbB 2 and / or erbB 4 ) , p42 / 44 ERK , and PKC . . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
METHODS : Bronchial biopsies obtained from non smokers ( n = 10 ) and current smokers , with or without chronic obstructive pulmonary disease ( n = 51 ) , were examined immunohistochemically to measure the expression of epidermal growth factor receptor , ErbB 2 , ErbB 3 , ErbB 4 and mucin subtypes ( MUC 2 , MUC5AC and MUC5B ) in the bronchial epithelium . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The erbB receptor family ( EGFr , erbB 2 , erbB 3 , and erbB 4 ) consists of transmembrane glycoproteins that transduce extracellular signals to the nucleus when activated . erbB family members are widely expressed in epithelial , mesenchymal , and neuronal cells and contribute to the proliferation , differentiation , migration , and survival of these cell types . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The ErbB family , ErbB 1 ( also known as the epidermal growth factor receptor EGFR ) , ErbB 2 , ErbB 3 , and ErbB 4 comprise a group of receptor tyrosine kinases that interact with ligands from the epidermal growth factor ( EGF ) superfamily , subsequently dimerize , catalytically activate each other by cross phosphorylation , and then stimulate various signaling pathways . ^^^ EGFR , ErbB 2 , and ErbB 4 exhibited distinct but sometimes overlapping distributions in multiple cell types within germinal zones , cortex , striatum , and hippocampus in prenatal and postnatal development . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Neuregulin receptors erbB 2 and erbB 4 in failing human myocardium depressed expression and attenuated activation . ^^^ In cultured cardiomyocytes , erbB 2 and erbB 4 receptors regulate apoptosis by controlling bcl 10 splicing , and conditional elimination of erbB 2 induces dilative cardiomyopathy in vivo . ^^^ ErbB receptors , expressed in cardiomyocytes and noncardiomyocytes , are downregulated in failing myocardium as mRNA ( which is renormalized by hemodynamic unloading ) and as protein ( erbB 2 : 25 % ; erbB 4 : 70 % ) , their phosphorylation is reduced and bcl 10 splicing is shifted towards 6 . 7 fold augmentation of proapoptotic Bcl xS , compatible with attenuated erbB signaling . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Here , we demonstrate that ErbB 2 , ErbB 3 and ErbB 4 are expressed in cultured human melanocytes . ^^^ Two malignant melanoma cell lines expressed ErbB 2 and ErbB 3 , but not the full length ErbB 4 receptor . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
ErbB 1 and ErbB 2 receptors are well characterized targets for anticancer drugs , but the clinical relevance of the related ErbB 4 receptor is unknown . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Using antibodies specific for the erbB receptors , we demonstrate the expression patterns for the erbB 2 , erbB 3 , and erbB 4 receptors in human glioma biopsy samples . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The expression of EGF receptors ( ErbB 1 and ErbB 2 , but not ErbB 3 or ErbB 4 ) was down regulated significantly in the same forebrain regions . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
At baseline , Western Blot analysis demonstrated expression of erbB 2 , erbB 3 and erbB 4 receptors and multiple NRG isoforms . ^^^ Following 1 and 8 weeks of PRT , no changes erbB 2 , erbB 4 or NRG expression were observed . ^^^ Thus , erbB 2 , erbB 3 , erbB 4 and multiple NRG isoforms are natively expressed in human skeletal muscle . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
PATIENTS AND METHODS : EGFR , ERBB 2 , ERBB 3 and ERBB 4 were evaluated immunohistochemically in normal urothelium ( NU , 15 ) , primary non metastasized invasive TCC ( NMC , 19 ) and in primary invasive TCCs with corresponding metastases ( MC , 51 , both specimens ) . ^^^ RESULTS : All NU samples expressed ERBB 4 , none expressed ERBB 2 and two expressed EGFR ; all staining was uniform throughout all cell layers . ^^^ ERBB 2 expression increased and ERBB 4 decreased from normal samples to carcinomas . ^^^ There was no difference between NMCs and MCs in ERBB 2 , ERBB 3 and ERBB 4 , but the NMCs expressed more EGFR than both NU and MC samples . ^^^ CONCLUSION : We hypothesise that : ( 1 ) ERBB 4 is important for differentiation in NU ; ( 2 ) ERBB 2 is up regulated with carcinogenesis in the urinary bladder but does not discriminate between bladder cancer with or without metastases ; ( 3 ) EGFR may be a marker of indolent disease . ^^^
Interacting proteins: Q15303 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: Q15303 and P04626	Pubmed	SVM Score :0.0
Culture on matrigel resulted in 11 fold increase in mRNA levels for ErbB 1 and ErbB 2 , and a 221 fold and 85 fold increase in the mRNA levels for ErbB 3 and ErbB 4 , respectively . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Treatment of astrocytes , however , with heregulin , which signals through other members of the EGF receptor family ( ErbB 2 , ErbB 3 , ErbB 4 ) , did not induce CSPG upregulation . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Transmembrane neuregulin expression was accompanied by constitutive activation of ErbB 2 , ErbB 3 , and ErbB 4 receptors . ^^^ ErbB 2 overexpression caused tyrosine phosphorylation of ErbB 2 , whereas ErbB 3 and ErbB 4 were only slightly tyrosine phosphorylated . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Baseline erbB 3 and erbB 4 revealed the highest frequencies of expression , while erbB 2 was the lowest . ^^^ At 50 mg / d , CI 1033 had a more favorable adverse events profile than at 200 mg / d . erbB 3 and erbB 4 receptors showed the highest expression in tumor samples while erbB 2 revealed the least . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
EGFR activation can also result in transphosphorylation of tyrosine resides in the C terminal region of the related receptors ErbB 2 , ErbB 3 and ErbB 4 in heterodimers which are formed upon ligand stimulation . ^^^ Our results demonstrated that ( 1 ) EGFR kinase can efficiently phosphorylate a broad range of diverse peptide sequences representing ErbB sites ; ( 2 ) certain ErbB 2 , ErbB 3 and ErbB 4 sites had higher specificity constants than any EGFR sequence and ( 3 ) EGF stimulation consistently increases the k ( cat ) approx . 5 fold , but does not significantly alter the K ( m ) for any ErbB peptides . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The human ErbB family of receptor tyrosine kinases comprises the epidermal growth factor receptor ( EGFR / ErbB1 / HER1 ) , ErbB 2 ( HER2 / Neu ) , ErbB 3 ( HER 3 ) , and ErbB 4 ( HER 4 ) . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
To evaluate the prognostic impact of the ErbB receptors expression profile , we analyzed a well characterized series of 145 primary breast carcinomas for the simultaneous expression of epidermal growth factor receptor ( EGFR / HER 1 ) , ErbB 2 ( HER 2 ) , ErbB 3 ( HER 3 ) , and ErbB 4 ( HER 4 ) , using immunohistochemistry . ^^^ Expression of EGFR , ErbB 2 , ErbB 3 , and ErbB 4 was observed in 31 ( 21 . 4 % ) , 65 ( 44 . 8 % ) , 72 ( 49 . 7 % ) , and 81 ( 55 . 9 % ) of the cases , respectively . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The ErbB 1 and ErbB 2 receptors are oncogenes with therapeutic significance in human cancer , whereas the transforming potential of the related ErbB 4 receptor has remained controversial . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Gain of function analyses show that EGFR , ErbB 2 , and ErbB 4 induce ectopic tumor like cell mass that contains increased numbers of mitotic cells . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The EGFR is a member of the ErbB receptor tyrosine kinase ( TK ) family , which also includes ErbB 2 ( HER2 / neu ) , ErbB 3 ( HER 3 ) , and ErbB 4 ( HER 4 ) . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Phosphorylated ERBB 2 correlated with EGFR and ERBB 2 , and inversely with oestrogen receptor ( ER ) , progesterone receptor ( PgR ) and ERBB 4 expression levels . ^^^
Interacting proteins: Q15303 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 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Six genes were over expressed ( ERBB 2 , TGFA , HB EGF , AREG , EREG and EPGN ) , 3 were under expressed ( ERBB 1 , ERBB 4 and NRG 4 ) and 2 were over or under expressed ( ERBB 3 and BTC ) . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Expression of ErbB 4 receptor is correlated with the incidence of non metastatic types of human cancers , whereas the overexpression of other ErbB receptor families ( ErbB1 / EGFR , ErbB 2 and ErbB 3 ) is correlated to the formation of metastatic tumors . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Structure activity relationships for inhibition of erbB 1 , erbB 2 , and erbB 4 were determined for a series of alkynamide analogues of quinazoline and pyrido [ 3 , 4 d ] pyrimidine based compounds . ^^^ The compounds showed pan erbB enzyme inhibition but were on average about 10 fold more potent against erbB 1 than against erbB 2 and erbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The inappropriate activation of one or more members of the ErbB family of receptor tyrosine kinases [ ErbB 1 ( EGFR ) , ErbB 2 , ErbB 3 , ErbB 4 ] has been linked with oncogenesis . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Analysis of tumor derived endothelial cells showed that they express EGFR , ErbB 2 , and ErbB 4 , whereas their normal counterparts express ErbB 2 , ErbB 3 , and ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
ErbB 1 is followed by ErbB 3 , ErbB 2 and ErbB 4 in MCF 7 at both the protein and mRNA levels . ^^^ In MDA MB 231 cells , ErbB 1 is followed by ErbB 2 , ErbB 4 and ErbB 3 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Whereas the epidermal growth factor receptor , ErbB 2 and ErbB 3 are positively associated with various cancers , clinical studies of ErbB 4 in breast cancer are contradictory . ^^^ Results from tissue culture analyses and some clinical studies suggested that ErbB 4 is either a tumor suppressor or is a negative regulator of ErbB 2 driven tumors . ^^^
Interacting proteins: Q15303 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 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
This ALISA has been shown to be specific for epidermal growth factor receptor ( EGFR ) and the isoforms of EGFR encoded by alternate transcripts ( i . e . , sEGFRs ) ; it , therefore , does not detect other EGFR / ErbB receptor family members , i . e . , ErbB 2 , ErbB 3 , or ErbB 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Here we show that , besides ErbB 3 , all CCSST cell lines ( n = 8 ) also express the ErbB 2 receptor or the ErbB 4 receptor , representing an adequate coreceptor of ErbB 3 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The fusion protein was found to induce receptor tyrosine phosphorylation in CEM cells transfected with HER 4 alone or in combination with HER 2 but not in cells transfected with HER 2 or HER 1 alone . ^^^ Relative amounts of HER 4 , HER 3 , and HER 2 were determined on seven cell lines sensitive and four cell lines insensitive to HAR TX beta 2 . ^^^ HAR TX beta 2 was able to bind to and signal via tyrosine phosphorylation in cell lines that co express HER 2 and HER 3 in the absence of HER 4 without inducing cytotoxicity . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Recently , it has been shown that HER 2 alone is not sufficient to reconstitute high affinity heregulin receptors and that HER 3 or HER 4 may be the required components of the heregulin receptors on mammary carcinoma cells ( Sliwkowski , M . ^^^ In contrast , the ovarian cells expressing high levels of HER 2 and low levels of HER 4 or CHO K 1 and 293 EBNA cells expressing HER 2 alone were not responsive to heregulin . ^^^
Interacting proteins: Q15303 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 . ^^^
Interacting proteins: Q15303 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 . ^^^ 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 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
This group includes the epidermal growth factor receptors , the HER 2 / neu ( erbB 2 ) , HER 3 , and HER 4 . ^^^ Despite the structural similarity of these receptors , HER 2 / neu , HER 4 , and HER 3 do not bind to any ligand of the epidermal growth factor receptor . ^^^ This ligand phosphorylates the HER 2 / neu receptor and binds directly to HER 4 and HER 3 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
We studied 19 medullary carcinomas for expression of the intercellular adhesion molecule 1 and lymphocyte function associated antigen 1 , Neu differentiation factor , tumor necrosis factor alpha , and the expression of HER 2 / neu , HER 4 , and HER 3 receptors . ^^^ By comparison , in a control group of infiltrating ductal carcinomas , expression of intercellular adhesion molecule 1 , lymphocyte function associated antigen 1 , and Neu differentiation factor was positive in about 25 to 30 % of the cases , HER 4 was expressed in 75 % and HER 3 in 95 % of the cases . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Furthermore , this heparin binding protein induces phenotypic differentiation , and tyrosine phosphorylation , of a human mammary tumor cell line that overexpresses both HER 4 and HER 2 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
We also determined the relationship of Neu , phosphorylated Neu ( and epidermal growth factor receptor ) , and phosphotyrosine to the expression of Neu related receptors ( epidermal growth factor receptor , HER 3 , and HER 4 ) and to prognostic factors ( estrogen and progesterone receptor ) . ^^^ Neu and HER 4 were associated with divergent correlates , suggesting that they have profoundly different biological activities . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Transformation of NIH 3T3 cells by HER 3 or HER 4 receptors requires the presence of HER 1 or HER 2 . ^^^ However , NDF induced cell transformation was observed when either HER 1 or HER 2 was coexpressed with HER 3 or HER 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Some of the mAbs strongly induced tyrosine phosphorylation of 180 185 kDa proteins , including not only Her 2 but also Her 3 and Her 4 receptors , when they were expressed on the surface of breast cancer cells . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Transfection of oncogenic neu ( Tneu ) , conferred ligand independent transformation only in cells which co expressed HER 1 , HER 3 , or HER 4 , but not when expressed alone or with HER 2 . ^^^ Although unable to form tumors when expressed alone , HER 2 was tumorigenic when expressed with HER 1 or HER 3 , but not HER 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
In vitro treatment of HER 2 and HER 3 or HER 2 and HER 4 expressing breast cancer cells stimulates tyrosine phosphorylation of HER 2 and produces changes in the rate of proliferation , degree of cellular differentiation , and synthesis of physiologic secretion products . ^^^ METHODS : Expression of NDF , HER 2 , HER 3 , and HER 4 was studied in 24 frozen prostatectomy specimens by immunohistochemistry . ^^^ Benign prostate tissue exhibits strong expression of HER 2 , HER 3 , and HER 4 by basal cells , but only luminal cells significantly express HER 4 . ^^^ Only 23 % of prostate cancer specimens express HER 4 , while 95 % express HER 3 and 82 % HER 2 . ^^^ 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 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Prognostic significance of HER 2 and HER 4 coexpression in childhood medulloblastoma . ^^^ In a series of 70 patients with childhood medulloblastoma , we have used immunohistochemistry and Western blotting analysis to investigate the expression patterns of all four EGFR family members ( EGFR , HER 2 , HER 3 , and HER 4 ) and heregulin alpha , a ligand for the HER 3 and HER 4 receptors . ^^^ The majority of cases expressed two or more receptor proteins ; coexpression of the HER 2 and HER 4 receptors occurred in 54 % . ^^^ To investigate whether coexpression results in receptor heterodimerization , we have also performed immunoprecipitation analysis of protein extracts from primary tumors , and we demonstrate various patterns of receptor interaction including between HER 2 and HER 4 . ^^^ In contrast , when considered together in the multivariate model , coexpression of HER 2 and HER 4 demonstrated independent prognostic significance ( P = 0 . 006 ) . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The EGF like growth hormone heregulin is a ligand for the HER 3 and HER 4 receptors and their heterodimers with HER 2 . ^^^ 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: Q15303 and P04626	Pubmed	SVM Score :0.0
Heregulin beta 2 , a naturally occurring ligand that activates the HER 2 receptor by inducing its heterodimerization with the HER 4 receptor , has recently been cloned . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Members of the epidermal growth factor receptor family of tyrosine kinases , including epidermal growth factor receptor , c erbB 2 ( HER 2 ) , c erbB 3 ( HER 3 ) , and c erbB 4 ( HER 4 ) , can be coexpressed at different levels in nonhematopoietic tissues . ^^^ 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 . ^^^ To evaluate the relative importance of HER 3 and HER 4 , NIH 3T3 cells were cotransfected with HER 2 and HER 3 or with HER 2 and HER 4 . ^^^ In cells that express only HER 2 and HER 4 , HRG stimulated the growth of cells that expressed HER 4 independent of HER 2 levels . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The human epidermal growth factor receptors 2 , 3 , and 4 ( HER 2 , HER 3 , and HER 4 , respectively ) are frequently overexpressed in many human cancers , and therefore may be potential targets for receptor mediated gene transfer . ^^^ 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 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Ligand dependent activation of HER 1 , HER 3 , and HER 4 by EGF or heregulin results in heterodimerization and , thereby , HER 2 activation . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
In a series of 111 patients with squamous cell carcinoma ( SCC ) , we used immunohistochemistry to examine the expression levels of four epidermal growth factor receptor ( EGFR ) family members ( EGFR , HER 2 / neu , HER 3 , and HER 4 ) . ^^^ Furthermore , the combination of HER 2 , HER 3 , and EGFR but not HER 4 significantly improved the predicting power . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Anti HER 2 antibodies bind to HER 2 directly , whereas heregulin does not bind to HER 2 alone , but rather interacts with HER 2 through the formation of heterodimers with HER 3 or HER 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The ability of the epidermal growth factor receptor ( EGFR ) family members , EGFR , HER 2 , HER 3 , and HER 4 , to form homo and heterodimers after interaction with different ligands expands the signal diversity of these proteins . ^^^ Consistently the predominant interaction after EGF treatment was between EGFR and HER 2 , whereas activation of HER 3 and HER 4 depended on the relative abundance of the four receptors in the cells . ^^^ 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: Q15303 and P04626	Pubmed	SVM Score :0.0
Moreover , we show that the sequence specific to the HER 4 JM a juxtamembrane region is sufficient to confer susceptibility to phorbol 12 myristate 13 acetate induced cleavage of the HER 2 receptor . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The human epidermal growth factor receptor ( HER ) family consists of four distinct receptors : HER 1 ( epidermal growth factor receptor ) , HER 2 , HER 3 , and HER 4 . ^^^ HER 2 and HER 3 messenger RNA and protein were detected in the fetal lung , but HER 4 expression was not detected . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Five human rhabdomyosarcoma cell lines were used to investigate the surface expression of HER / erbB receptors , particularly of HER 2 , HER 3 and HER 4 , by flow cytometry . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Our understanding of the normal signaling mechanisms and functions of human epidermal growth factor receptor 2 ( HER 2 ) and other members of the HER family , namely epidermal growth factor receptor , HER 3 , and HER 4 , is growing rapidly . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Coexpression patterns of EGFR , HER 2 , HER 3 and HER 4 in non melanoma skin cancer . ^^^ The receptor tyrosine kinases ( RTKs ) epidermal growth factor receptor ( EGFR ) , HER 2 , HER 3 and HER 4 are involved in the pathogenesis of multiple human malignant neoplasias . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Ligand dependent heterodimerization between HER 2 and another HER family member , HER 1 , HER 3 or HER 4 , activates the HER 2 signaling pathway . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Using in vitro models , recent studies have shown that HER 2 overexpression may not be a prerequisite for invasion of breast cancer cells , as HER 2 activation by heregulin , which binds to HER 3 or HER 4 and transphosphorylates HER in noninvasive breast cancer cells , could lead to increased motility , enhanced gelatinolytic activity , and invasion . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
In the cell lines with either endogenously ( SUM 44 ) or exogenously ( SUM 102 ) expressed HER 4 , elimination of HER 2 did not alter HER 4 dependent decreases in cell growth . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Ligand binding to HERI , HER 3 or HER 4 induces rapid receptor dimerization , with a marked preference for HER 2 as a dimer partner . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Six out of 11 human pancreatic cancer cell lines expressed all four epidermal growth factor ( EGF ) receptor family members ( HER 1 ( EGF R ) , HER 2 , HER 3 , and HER 4 ) , including Panc 89 cells . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The frequency of expression was : EGFR ( 51 % ) , HER 2 ( 54 % ) , P HER 2 ( 48 % ) , HER 3 ( 48 % ) , HER 4 ( 57 % ) , heregulin ( 48 % ) , p 38 ( 17 % ) , MAPK ( 48 % ) . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Cancer cell invasiveness can be promoted , even in the absence of HER 2 overexpression , by transregulation of HER 2 by heregulins that bind to HER 3 and HER 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
While HER 1 ( EGF receptor ) and HER 2 have been extensively studied , little is known about the clinical significance of HER 3 and especially HER 4 expression . ^^^ METHODS : We investigated the expression of HER 1 , HER 2 , HER 3 and HER 4 in 11 pancreatic cancer cell lines using FACS analysis and determined expression and overexpression of these receptors in 24 pancreatic cancer specimens . ^^^ RESULTS : HER 1 and HER 2 were expressed by all 11 pancreatic cancer cell lines , HER 3 was found in 82 % and HER 4 in 54 % of the cell lines . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Because ZD 1839 does not inhibit the HER 2 tyrosine kinase in vitro , and because heregulin is a ligand that activates HER 2 by binding to HER 3 and HER 4 but does not bind to the EGFR , our findings suggested that ZD 1839 interfered with HER 2 function in intact cells . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Many cell types express multiple EGFR family members ( including EGFR , HER 2 , HER 3 , and / or HER 4 ) that interact to form an array of homo and heterodimers . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The EGF Receptor ( EGFR ) , the first transmembrane receptor tyrosine kinase cloned and sequenced , and its closely related family members HER 2 , HER 3 , and HER 4 , play myriad roles in mammalian growth and development . ^^^ This signaling system ' s impact on human neoplasia is underscored by the following : i . ) EGFR is overexpressed or activated by autocrine or paracrine growth factor loops in at least 50 % of epithelial malignancies ; ii . ) HER 2 is amplified and dramatically overexpressed in approximately 20 % 25 % or breast cancers ; 3 ) HER 3 and HER 4 are variably expressed in breast and other cancers . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Moreover , transfer of non tumor specific T cells in combination with the fusion proteins , induced the eradication of established Her 2 , Her 3 , and Her 4 expressing tumor cells in SCID mice . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
This proteomic study allowed identification of the following proteins : human receptor protein kinase HER 2 or ERBB 2 and related kinases HER 3 and HER 4 , the gene products from breast cancer type 1 and 2 susceptibility genes and cytoskeletal components such as cytokeratins 8 , 18 and 19 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Elevated expression of HER 1 was observed in 16 . 4 % , HER 2 in 22 . 8 % , HER 3 in 17 . 5 % , and HER 4 in 11 . 9 % of these tumours . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Although the mRNA levels of HER family genes analyzed by RT PCR were significantly lower in myeloma cells than breast cancer cells , some cell lines expressed a certain amount of HER 2 and HER 4 proteins . ^^^
Interacting proteins: Q15303 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 . ^^^ We did not observe a correlation between EGFR and Her 2 / neu or Her 4 protein expression , EGFR and Her 3 ( p = 0 . 005 ) , and Her 3 and Her 4 ( p = 0 . 05 ) were clearly co expressed . ^^^ The strongest overall correlation , was found between Her 2 / neu and Her 3 ( p < 0 . 001 ) and between Her 2 / neu and Her 4 ( p = 0 . 001 ) . ^^^ This was particularly true in nodal positive tumors ( p < 0 . 001 and p = 0 . 002 ) whereas in nodal negative tumors the co expression was either less significant ( Her 2 / neu and Her 3 ; p = 0 . 01 ) or not significant ( Her 2 / neu and Her 4 ) . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Adenosine anchored triphosphate subsite probing : distinguishing between HER 2 and HER 4 tyrosine protein kinases . ^^^ A strategy of full site occupancy and stereospecific recognition in the triphosphate subsite was used to specifically inhibit two protein kinases HER 2 and HER 4 from the EGFR family . ^^^ The SAR profiles of a panel of adenosine anchored bicyclic heterocycles against HER 2 and HER 4 indicated that specificity can be derived for highly homologous protein kinases from stereospecific recognition in the triphosphate subsite . . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Analysis of HER 2 and HER 4 in human myocardium to clarify the cardiotoxicity of trastuzumab ( Herceptin ) . ^^^ To clarify whether myocardial HER 2 and HER 4 expression in response to anthracycline exposure and cardiac damage contributes to cardiotoxicity , we assessed expression of HER 2 and HER 4 in pathologically altered myocardium . ^^^ Expression of HER 2 and HER 4 was analyzed immunohistochemically ( HER 2 : HercepTest / A0485 ( Dako ) , Cy 3 detection ( Dianova ) ; HER 4 : Ab 4 ( NeoMarkers ) ) . ^^^ CONCLUSIONS : Cardiac alterations are not associated with an strong increase in HER 2 and HER 4 levels . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
All four known subgroups of the EGFR family were determined by immunohistochemistry ( IHC ) : c erbB 1 ( EGFR ) , c erbB 2 ( HER2 / neu ) , c erbB 3 ( HER 3 ) and c erbB 4 ( HER 4 ) . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The various cell lines expressed different levels of EGFR , HER 2 , HER 3 , and HER 4 , but there was no correlation between levels of EGFR and / or HER 2 expression and drug sensitivity . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
BACKGROUND : We have shown previously that whereas overexpression of human epidermal growth factor receptor ( HER ) 1 , HER 2 and HER 3 is associated with poor prognosis in breast cancer , HER 4 is associated with a good prognosis . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
While it is well established that an increased signalling through HER 1 and HER 2 is related to a poor prognosis , our data suggest that signalling through HER 3 and HER 4 is related to a favourable outcome in bladder cancer patients . . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
HER 2 ( human epidermal growth factor receptor 2 ; also known as erbB 2 ) and its relatives HER 1 ( epidermal growth factor receptor ; EGFR ) , HER 3 and HER 4 belong to the HER family of receptor tyrosine kinases . ^^^ HER 2 ( human epidermal growth factor receptor 2 ; also known as erbB 2 ) and its relatives HER 1 ( epidermal growth factor receptor ; EGFR ) , HER 3 and HER 4 belong to the HER family of receptor tyrosine kinases . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Promising approaches and molecular markers include gene expression profiles , DNA ploidy , loss of heterozygosity and chromosomal aberrations as detected by CGH and FISH ( 1q , 17p , 17q ) , as well as oncogenes / tumor suppressor genes and their proteins ( TP 53 , PTEN , c erbB 2 , N myc , c myc ) , growth factor and hormonal receptors ( PDGFRA , VEGF , EGFR , HER 2 , HER 4 , ErbB 2 , hTERT , TrkC ) , cell cycle genes ( p 27 ) and cell adhesion molecules , as well as factors potentially related to therapeutic resistance ( multi drug resistance , DNA topoisomerase IIalpha , metallothionein , P glycoprotein , tenascin ) . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Potentially prognostic histopathological markers vary among different entities and consist of assessment of necroses , mitoses , differentiation , vascular proliferation , and growth pattern , whereas immunohistochemical features include proliferation markers ( Ki 67 , MIB 1 ) , expression of oncogenes / tumor suppressor genes and their proteins ( TP 53 , c erbB 2 ) , growth factor and hormonal receptors ( VEGF , EGFR , HER 2 , HER 4 , ErbB 2 ) , cell cycle genes ( p 27 , p14ARF ) and cell adhesion molecules , as well as factors potentially related to therapeutic resistance ( DNA topoisomerase IIalpha , metallothionein , P glycoprotein , tenascin ) . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The growth of colon ( HCT 116 , Caco 2 , and HT 29 ) and breast ( MDA MB 468 and SKBR 3 ) cancer cells expressing varying levels of EGFR , HER 2 , and / or HER 4 was inhibited by recombinant ERRP in a dose dependent manner . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The expressions of different epidermal growth factor receptors such as EGFR ( HER 1 ) , HER 2 , HER 3 , and HER 4 have not yet been examined in these tumors . ^^^ Twenty three cases of endometrial sarcomas consisting of 20 low grade endometrial stromal sarcomas and 3 undifferentiated endometrial sarcomas were examined immunohistochemically for EGFR ( HER 1 ) , HER 2 , HER 3 , and HER 4 . ^^^ All examined cases were negative for HER 2 , HER 3 , and HER 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The objective of the current study was to determine the frequency and the possible prognostic effect of coexpression of HER 1 , HER 2 , HER 3 , and HER 4 by breast carcinoma . ^^^ RESULTS : Using univariate analysis , expression of HER 1 , HER 2 , and HER 3 , but not HER 4 , was significantly associated with decreased patient disease specific survival ( P < 0 . 05 ) . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The type 1 tyrosine kinase receptor HER 2 ( c erbB2 / neu ) is associated with resistance to hormone therapy and poor survival in invasive breast cancer , whereas HER 4 expression is associated with endocrine responsiveness . ^^^ Primary tumors were compared for HER 2 , HER 3 , and HER 4 , estrogen receptor , and Ki 67 by immunohistochemistry . ^^^ HER 2 was expressed in 58 % , HER 3 in 49 % , and HER 4 in 63 % of nonrecurrent DCIS , compared with HER 2 expression in 82 % ( P = 0 . 008 ) , HER 3 expression in 71 % ( P = 0 . 04 ) , and HER 4 expression in 36 % ( P = 0 . 004 ) in DCIS that subsequently recurred . ^^^ HER 2 expression was associated with a higher percentage and HER 4 expression a significantly lower percentage of proliferating DCIS cells ( median , 13 . 8 % versus 8 . 4 % ; P = 0 . 001 ) . ^^^ Coexpression of HER 2 with HER 4 was associated with reduced recurrence compared with HER 2 only positive DCIS ( P = 0 . 003 ) . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Expression of EGFR , HER 2 , HER 3 , and HER 4 in metastatic squamous cell carcinomas of the oral cavity and base of tongue . ^^^ HER 2 , HER 3 , and HER 4 were evaluated by immunohistochemistry in 19 cases of metastatic squamous cell carcinoma of the oral cavity and base of tongue . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The diverse signaling network of EGFR , HER 2 , HER 3 and HER 4 tyrosine kinase receptors and the consequences for therapeutic approaches . ^^^ There are clinical indications supporting the concept that none of the receptors : EGFR , HER 2 , HER 3 and HER 4 can be considered as the stand alone receptor in breast cancer development and clinical course of the disease . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
We previously demonstrated that primary osteosarcoma cells express cell surface EGFR and Her 2 , with the p 80 isoform of Her 4 localized to the nucleus . ^^^ PROCEDURES : We cultured early passage osteosarcoma cell lines in the presence or absence of the pan erbB inhibitor CI 1033 and examined the phosphorylation status of EGFR , Her 2 , and Her 4 by immunohistochemistry , cell based ELISA , flow cytometry and two dimensional Western blot . ^^^ RESULTS : EGFR , Her 2 , and Her 4 were constitutively phosphorylated in early passage osteosarcoma cells cultured in vitro . ^^^ CONCLUSIONS : EGFR , Her 2 , and Her 4 are constitutively phosphorylated in early passage osteosarcoma cells in tissue culture , and erbB signaling provides essential growth and anti apoptotic signals to osteosarcoma cells . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
JIMT 1 cells overexpress HER 2 mRNA and protein , and the levels of HER 1 , HER 3 , and HER 4 mRNA and protein were similar to the trastuzumab sensitive cell line SKBR 3 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Neuregulins constitute a family of EGF like ligands that bind to HER 3 or HER 4 , preferably forming heterodimers with the orphan receptor HER 2 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The results demonstrated the presence of c erbB 2 ( HER 2 ) and c erbB 4 ( HER 4 ) in 10 to 50 % of the neoplastic cells of high grade glial tumors with high immunoreactivity , while c erbB 3 ( HER 3 ) was only detected in less than 10 % of the neoplastically transformed cells . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Human EGF Receptor 1 ( HER 1 ) showed highest expression during the proliferative phase , HER 2 and HER 4 during the early and HER 3 during the late secretory phase . ^^^ HER 1 , HER 2 , HER 3 and HER 4 were localized to the epithelium and glands HER 3 and HER 4 solely in the secretory phase . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Our study suggest that , in primary prostate cancer , HER 3 , together or not with HER 4 , rather than in receptor complexes involving HER 2 , could play an important role in the biology of these tumors . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
OBJECTIVE : To investigate prognostic significance of and correlations between HER 1 ( EGFR ) , HER 2 ( c erb B 2 ) , HER 3 ( c erb B 3 ) , HER 4 ( c erb B 4 ) , and phosphorylated Akt ( P Akt ) in patients treated with radiation for cervical carcinoma . ^^^ Correlation between human epidermal growth factor receptor family ( EGFR , HER 2 , HER 3 , HER 4 ) , phosphorylated Akt ( P Akt ) , and clinical outcomes after radiation therapy in carcinoma of the cervix . ^^^ RESULTS : Correlations were observed between expression of HER 2 and HER 4 ( P = 0 . 003 ) , and HER 3 and HER 4 ( P = 0 . 004 ) . ^^^ Decreased HER 2 , HER 4 , and P Akt expressions were significant for diminished DFS on univariate analysis ( P = 0 . 04 , P = 0 . 008 , and P = 0 . 02 , respectively ) . ^^^ Increased EGFR , and diminished HER 2 , HER 4 , and P Akt expression were significant or showed trends toward significance for diminished OS on univariate analysis ( P = 0 . 07 , P = 0 . 008 , P = 0 . 09 , and P = 0 . 08 , respectively ) . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
In culture ZD 1839 inhibited the growth of four NSCLC cell lines ( A 549 , NCI H 23 , NCI H 727 , and NCI H 661 ) that expressed various levels of EGFR , HER 2 , HER 3 , and HER 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
HER 2 is a ligand less member of the HER family that functions as the preferred coreceptor for epidermal growth factor receptor ( EGFR ) , HER 3 , and HER 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
METHODS : The immunohistochemical expression of EGFR ( Her 1 ) , Her 2 , Her 3 , and Her 4 was analyzed in a group of ovarian GCTs encompassing 38 adult type and 2 juvenile type . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Although clinically effective monoclonal antibodies ( MAbs ) have been developed to target HER 2 and EGFR , the remaining two family members , HER 3 and HER 4 , have not been the subject of significant efforts . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Investigation of about 60 loci containing genes associated with the epidermal growth factor family ( epidermal growth factor receptor , HER 2 , HER 3 and HER 4 ) revealed that all seven cell lines harbor copy number changes to multiple genes in these pathways . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
The relation between survival and expression of HER 1 and HER 2 depends on the expression of HER 3 and HER 4 : a study in bladder cancer patients . ^^^ Also , a significantly longer survival was observed in patients expressing high HER 2 when coexpressed with high HER 3 and HER 4 , as compared to the survival in patients with tumours expressing high HER 2 but low HER 3 and HER 4 ( P=0 . 0005 ) . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
In this study we compared Qrt PCR results for the assessment of mRNA levels of ERa , PgR , and the members of the human epidermal growth factor receptor family , HER 1 , HER 2 , HER 3 and HER 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
Pertuzumab ( rhuMAb 2C4 ) , a humanized HER 2 antibody , represents a new class of targeted therapeutics that inhibit dimerization of HER 2 with ligand activated EGFR ( HER 1 ) , HER 3 , and HER 4 . ^^^
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
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Interacting proteins: Q15303 and P04626	Pubmed	SVM Score :0.0
NA