Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.53570045
Interaction of heparin binding EGF like growth factor ( HB EGF ) with the epidermal growth factor receptor : modulation by heparin , heparinase , or synthetic heparin binding HB EGF fragments . 0.53570045^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.62024359
These results suggested that adhesion between blastocysts and cells synthesizing HB EGF TM was mediated via interaction with both blastocyst EGFR and heparan sulfate proteoglycan ( HSPG ) . 0.62024359^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.52434251
Each member of the group formed by BTC , heparin binding EGF ( HB EGF ) and epiregulin ( EP ) can interact with both the EGF receptor ( EGFR ) and heregulin receptors ( ErbB 3 and ErbB 4 ) , and are hence called `` bispecific ' ' ligands . 0.52434251^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
This EGF receptor ( EGF R ) binding property was abolished by an antiserum to heparin binding EGF like growth factor ( HB EGF ) that specifically blocks binding of HB EGF to the EGF R . ^^^ Reverse phase HPLC resulted in the purification of two EGF R binding activities correlated with 13 , 500 and 17 , 000 M ( r ) proteins that reacted with an antiserum raised against residues 9 26 of human HB EGF . ^^^ Uterine extracts also contained an EGF R binding factor that was eluted from heparin by 1 . 0 M NaCl and was antagonized by HB EGF antiserum . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Heparin binding EGF ( HB EGF ) , a newly discovered member of the EGF family of mitogens , binds to the EGF receptor ( EGFR ) and to heparan sulfate proteoglycans on the cell surface . ^^^ Here , we show that the binding of HB EGF to the EGFR is inhibited by mAbs which prevent the interaction of EGF and TGF alpha with the receptor . ^^^ Also , we show that , like EGF and TGF alpha , treatment with HB EGF inhibits the growth in vitro of tumours ( HN 5 , HSC 4 ) that overexpress the EGFR . ^^^ We conclude that mAbs which act as EGF and TGF alpha antagonists should also be effective therapeutic agents for blocking the growth of EGFR overexpressing tumours induced by HB EGF . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
HB EGF can bind to two loci on cell surfaces , heparan sulphate proteoglycans and EGF receptor ( EGF R ) , and either one or both of these interactions could play a role in cell cell interactions . ^^^ In vitro studies showed that HB EGF induced blastocyst EGF R autophosphorylation , and promoted blastocyst growth , zona hatching and trophoblast outgrowth . ^^^ These results suggest possible interactions between the uterine HB EGF and blastocyst EGF R very early in the process of implantation , earlier than any other embryo uterine interactions defined to date at the molecular level . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
TGF alpha , AR , HB EGF , and EGF were equipotent in stimulating [ 3H ] thymidine incorporation by RIE 1 cells and bound the EGFr with equivalent affinity . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
This antibody effectively blocks the binding of EGF , transforming growth factor ( TGF ) alpha and HB EGF to the EGFR , inhibits the growth in vitro of tumour cell lines which overexpress the EGFR and eradicates such tumours when grown as xenografts in athymic mice . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
To assess the potential role of HB EGF in human gastric carcinomas , the expression of HB EGF and EGF receptor ( EGF R ) was examined in normal and cancerous gastric tissues and cultured gastric cancer cell lines . ^^^ Immunostaining revealed co localization in 72 % of the cancer cells of HB EGF and EGF R . ^^^ By Northern blot analysis , HB EGF , TGF alpha , AR , BTC and EGF R mRNA moieties were co expressed in KATO 3 and NCI N 87 gastric cancer cell lines . ^^^ Our findings suggest that HB EGF is relatively abundant in human gastric cancers and that co expression of the EGF ligand family may lead to excessive activation of EGF R in this disorder . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Consequently , only NDF , HB EGF , and BTC significantly stimulated association of phosphatidylinositol kinase activity with ErbB 3 . ^^^ Among the EGF agonists , HB EGF induced a low level of ErbB 4 tyrosine phosphorylation , while BTC was as efficient as NDF in activating ErbB 4 . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
We have investigated whether monoclonal antibodies ( mAbs ) to the EGFR which act as EGF , TGF alpha and HB EGF antagonists could also be effective as BTC antagonists by blocking its binding to the EGFR . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
EGF , TGF alpha , AR , and HB EGF all stimulated qualitatively similar patterns of erbB family receptor tyrosine phosphorylation and coupling to physiologic responses . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Heparin binding epidermal growth factor like growth factor ( HB EGF ) is a recently described member of the EGF family that binds to and stimulates phosphorylation of the EGF receptor ( EGFR ) . ^^^ In view of the wide expression of its cognitive receptor , EGFR , in central nervous system neurons , our results suggest that HB EGF is an endogenous ligand for EGFR in the central nervous system and may play an important role in physiological conditions . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
A strong immunostaining of EGFRs was observed in these SMCs , suggesting a close association of HB EGF and EGFR expression . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Furthermore , the epidermal growth factor receptor to which HB EGF can bind was also immunostained positively in neointimal SMCs . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Human pancreatic cancers over express the epidermal growth factor receptor ( EGF R ) and all 5 known ligands of the EGF family , including EGF , transforming growth factor alpha ( TGF alpha ) , amphiregulin , betacellulin and heparin binding EGF like growth factor ( HB EGF ) . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Amphiregulin ( AR ) and Heparin Binding EGF like growth factor ( HB EGF ) bind and activate the EGFR while Heregulin ( HRG ) acts through the p185erbB 2 and p180erbB 4 tyrosine kinases . ^^^ Indeed , upon activation with Phorbol 12 , 13 dibutyrate ( PDBu ) , the human monocytic like THP 1 cells expressed high levels of AR , HRG and HB EGF transcripts and released heparin binding factors that induced tyrosine phosphorylation of the EGFR in A 431 cells and a protein of 185 kDa in MDA MB 453 cells . ^^^
Interacting proteins: Q99075 and P00533	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 . ^^^ Finally , ErbB 1 activated by all EGF related peptides ( EGF , HB EGF , BTC and NDF ) couples to SHC , whereas only ErbB 1 activated by its own ligands associates with and phosphorylates Cbl . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Heparin binding EGF like growth factor ( HB EGF ) , a novel member of the EGF family , also binds to EGFR . ^^^ To compare the expression of HB EGF , TGF alpha and EGFR genes in NSCLC and normal lung tissue , we measured the levels of messenger RNA ( mRNA ) for these genes in human NSCLC and normal lung tissues by Northern hybridization , reverse transcription polymerase chain reaction ( RT PCR ) , and in situ hybridization . ^^^ HB EGF was not expressed in either tumor tissue or normal lung tissue , while EGFR and TGF alpha were expressed in all samples . ^^^ Our results showed that HB EGF plays no role in the growth of NSCLC , and that there was no significant overexpression of EGFR in tumor tissue . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Anti EGFR monoclonal antibodies which act as EGF , TGF alpha , HB EGF and BTC antagonists block the binding of epiregulin to EGFR expressing tumours . ^^^ We found that MAb ICR 9 , which enhances the binding of EGF , TGF alpha , HB EGF and betacellulin to the EGFR , also increases the binding of 125I epiregulin to a number of EGFR expressing tumour cell lines , including EJ , SKBR 3 , SKOV 3 , MDA MB 468 and HN 5 . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
The cultured human vascular SMCs and endothelial cells expressed both FGFR 1 and EGFR with predominant perinuclear localization . bFGF and HBEGF demonstrated equally potent mitogenic effects on SMC proliferation . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Finally , treatment of E 5 expressing cells with HB EGF shows no increased phosphorylation of the ErbB 4 receptor , suggesting a specific effect of E 5 on the activation of the different members of the EGFR family . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Thus , EGFR activation in SUM 102PT cells is mediated , at least in part , by autocrine / juxtacrine stimulation by HB EGF . ^^^ Thus , SUM 102PT is a new human breast cancer cell line that expresses activated EGFR as a result of an autocrine / juxtacrine interaction with HB EGF which , in turn , results in activation of STAT 3 . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Immunohistochemistry demonstrated that membrane anchored HB EGF ( proHB EGF ) and EGFR were co expressed in 44 % of 34 human malignant gliomas . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
The Epidermal Growth Factor Receptor ( EGF R ) and its ligands are potential components of the embryo maternal cross talk : Employing RT PCR , in situ hybridization , and immunohistochemistry , we investigated on mRNA and protein level the expression of EGF R , Epidermal Growth Factor ( EGF ) , Transforming Growth Factor alpha ( TGF alpha ) , and Heparin binding EGF like Growth Factor ( HB EGF ) in spherical and elongating bovine blastocysts between day 13 and day 16 of gestation , and in endometrium at day 13 of gestation . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
In 6 HCC cell lines , clear expressions of EGFR and TGF alpha were found in flow cytometry , while expressions of EGF , HB EGF and AR were quite low . ^^^ In non stimulated cultures , cell proliferation was suppressed by anti EGFR neutralizing antibody , but not by the antibodies for EGF , TGF alpha , AR and HB EGF . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Multiple epidermal growth factor receptor ( EGFr ) ligands have been identified , including transforming growth factor alpha ( TGFalpha ) , heparin binding epidermal growth factor ( HB EGF ) , amphiregulin ( AR ) , and betacellulin ( BTC ) . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
METHODS : Prior to sacrifice and assay of HB EGF and EGF receptor ( EGF R ) mRNA , morphologic and hemodynamic variables were measured in SHR and in age matched Wistar Kyoto rats ( WKY ) . ^^^ At 5 , 9 and 12 weeks of age , rats were killed , their hearts were removed , and the expression of HB EGF and EGF R mRNA and protein were measured . ^^^ Expression of HB EGF mRNA was also observed to peak in these animals at 9 weeks , while expression of EGF R mRNA increased from 5 to 9 weeks , but remained constant thereafter . ^^^ In untreated WKY , double products and EGF R mRNA expression did not change over time , whereas the level of HB EGF message increased gradually . ^^^ Antibody to HB EGF reacted primarily with myocyte membranes in SHR , whereas antibody to EGF R reacted mainly with interstitial cells in these animals . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
We have investigated the feasibility of using HBEGF to selectively deliver a cytotoxic protein into EGFR expressing tumor cells . ^^^ A construct with a 22 amino acid flexible linker ( L 22 ) between the HBEGF and SAP moieties exhibited an affinity for the EGFR that was comparable to that of HBEGF . ^^^ HBEGF L 22 SAP was cytotoxic in vitro to a variety of EGFR bearing cell lines and inhibited growth of EGFR over expressing human breast carcinoma cells in vivo . ^^^ Our results demonstrate that fusion proteins composed of HBEGF and SAP exhibit targeting specificity and cytotoxicity that may be of therapeutic value in treating a variety of EGFR bearing malignancies . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Cell specific activation of the HB EGF and ErbB 1 genes by stretch in primary human bladder cells . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Heparin binding epidermal growth factor like growth factor ( HB EGF ) transduces mitogenic signals through the EGF receptor ( EGFR ) . ^^^ We studied the biological activity of pro HB EGF by using a model in which pro HB EGF expressing effector cells was co cultured with EGFR expressing target cells . ^^^ This rules out the possibility of simple competition between soluble EGFR ligands and pro HB EGF . ^^^ Moreover , 32D cells expressing EGFR mutant composed of the extracellular and the transmembrane domain of EGFR and the cytoplasmic domain of erythropoietin receptor did not undergo apoptosis by co culture with Vero H cells , indicating that the inhibitory signal induced by pro HB EGF expressing Vero H cells is mediated to DER cells via EGFR and that the cytoplasmic domain of EGFR is essential for pro HB EGF induced apoptosis . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Expression levels of membrane anchored HB EGF ( proHB EGF ) protein were increased specifically during their differentiation among epidermal growth factor receptor ( EGFR ) ligands . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
TGF ( & agr ; ) or HB EGF binds to EGF receptor ( ErbB 1 ) , while HB EGF , in addition , binds to ErbB 4 . ^^^ The results indicate that ErbB 1 is inefficient in mediating TGF ( & agr ; ) PE or HB EGF PE toxicity as follows : ( 1 ) TGF ( & agr ; ) PE was relatively inferior in killing blastocysts , 100 fold less than HB EGF PE , ( 2 ) analysis of blastocysts isolated from cross bred egfr+ / mice demonstrated that HB EGF PE , but not TGF ( & agr ; ) PE , killed egfr / blastocysts , and ( 3 ) blastocysts that survived TGF ( & agr ; ) PE were nevertheless killed by HB EGF PE . ^^^ It is concluded that ( 1 ) HB EGF interacts with the blastocyst cell surface via high affinity receptors other than ErbB 1 , ( 2 ) the HB EGF interaction with high affinity blastocysts receptors is regulated by heparan sulfate , and ( 3 ) ErbB 4 is a candidate for being a high affinity receptor for HB EGF on the surface of implantation competent blastocysts . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
These results demonstrate that keratinocyte contact with type 1 collagen is sufficient to induce collagenase 1 expression , whereas sustained enzyme production requires autocrine EGFR activation by HB EGF as an obligatory intermediate step , thereby maintaining collagenase 1 dependent migration during the re epithelialization of epidermal wounds . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Upon activation by at least five genetically distinct ligands ( including EGF , transforming growth factor alpha ( TGF alpha ) and heparin binding EGF ( HB EGF ) ) , the intrinsic kinase is activated and EGFR tyrosyl phosphorylates itself and numerous intermediary effector molecules , including closely related c erbB receptor family members . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
The initial phase of screening and early detection is hoped to be better assessed by using molecular markers detecting gene mutations ( p 53 , K ras ) , growth factors ( EGF , TGF alpha , TGF beta , HB EGF , a / bFGFs , KGF ) and growth factor receptor alterations ( EGFr , c erbB2 / 3 / 4 ) . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Heparin binding epidermal growth factor ( HB EGF ) interacts with both EGF R and a related receptor , ErbB 4 , whereas transforming growth factor alpha ( TGFalpha ) interacts only with EGF R . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Heparin binding epidermal growth factor like growth factor ( HB EGF ) , an activating ligand for the epidermal growth factor receptor ( ErbB 1 ) tyrosine kinase and at least one isoform of the ErbB 4 receptor tyrosine kinase , is synthesized by the smooth muscle of the human bladder wall . ^^^ Human and mouse bladder SMC in vivo and cultured human bladder SMC expressed the primary HB EGF receptor , ErbB 1 , but not mRNA for the secondary HB EGF receptor , ErbB 4 , thereby identifying ErbB 1 as the cognate HB EGF receptor in the bladder wall . ^^^ Urethral ligation in mice resulted in an increase in steady state HB EGF mRNA expression up to 24 hours in whole bladder tissue in comparison with ErbB 1 and glyceraldehyde 3 phosphate dehydrogenase mRNA levels , which did not change in a demonstrable pattern . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
In this study , we compared expression levels of messenger RNAs ( mRNAs ) encoding the epidermal growth factor ( EGF ) receptor related receptor tyrosine kinases ( ErbB 1 through 4 ) , the six EGF receptor ligands , EGF , transforming growth factor ( TGF ) alpha , amphiregulin ( ARG ) , HB EGF , betacellulin , and epiregulin , and the related molecule heregulin alpha , in a series of 10 prostate tissue specimens . ^^^ ARG was immunolocalized largely to interstitial smooth muscle cells ( SMC ) , previously identified as the site of synthesis of HB EGF in the prostate , while the cognate ARG and HB EGF receptor , ErbB 1 , was localized exclusively to ductal epithelial cells and carcinoma cells . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
This study examines immunohistochemically the presence of EGF , TGFalpha , HB EGF , AR , and EGFR , members of the EGF family in the monkey uterus during the menstrual cycle and early pregnancy . ^^^ EGF , TGFalpha , HB EGF , AR , and EGFR were mainly localized in glandular and luminal epithelium . ^^^ The level of EGF , TGFalpha , HB EGF , AR , and EGFR staining was low on days 1 and 6 , and began to increase on day 9 of the menstrual cycle . ^^^ In early pregnancy , a low level of EGF , TGFalpha , HB EGF , AR , and EGFR staining appeared on days 1 and 2 of pregnancy , and then gradually increased from day 3 of pregnancy . ^^^ The highest levels of EGF , TGFalpha , HB EGF , and EGFR were detected on days 9 , and 11 of pregnancy . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
HB EGF both induced intracellular Ca2+ signaling and accelerated trophoblast development to an adhesion competent stage , but only late on gestation day 4 after ErbB 4 , a receptor for HB EGF , translocated from the cytoplasm to the apical surface of trophoblast cells . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Simultaneous quantitation of several mRNA species by calibrated reverse transcription polymerase chain reaction and capillary electrophoresis : analysis of the epidermal growth factor receptor and its activating ligands EGF , TGF alpha , and HB EGF in rat liver . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Of several ligands activating various ErbB receptors , including heregulin , neuregulin 3 , beta cellulin , heparin binding epidermal growth factor ( HB EGF ) , transforming growth factor alpha ( TGF alpha ) and EGF , heregulin shows the most potent mitogenic effects on supporting cells . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Although at first a ligand independent mechanism for EGFR transactivation was postulated , it has recently been shown that this transactivation by various G protein coupled receptor agonists can involve heparin binding EGF like growth factor ( HB EGF ) . ^^^ Because thrombin stimulation of vascular smooth muscle cell migration is blocked by heparin and because heparin can displace HB EGF , we investigated the possibility that thrombin stimulation of smooth muscle cells ( SMCs ) depends on EGFR activation by HB EGF . ^^^ In rat SMCs , EGFR phosphorylation and extracellular signal regulated kinase ( ERK ) activation in response to thrombin are inhibited not only by the EGFR inhibitor AG 1478 and by EGFR blocking antibody but also by heparin and by neutralizing HB EGF antibody . ^^^ We conclude from these data that the inhibitory effect of heparin on SMC migration induced by thrombin relies , at least in part , on a blockade of HB EGF mediated EGFR transactivation . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
We provide evidence here that wound stimuli induce keratinocyte shedding of EGFR ligands in vitro , particularly the ligand heparin binding EGF like growth factor ( HB EGF ) . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Estrogen induced activation of Erk 1 and Erk 2 requires the G protein coupled receptor homolog , GPR 30 , and occurs via trans activation of the epidermal growth factor receptor through release of HB EGF . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
EGFR mRNA was detected in all tumours , transforming growth factor alpha ( TGFalpha ) mRNA levels were similar to those in normal bladder urothelia or were decreased and mRNA levels for amphiregulin , heparin binding epidermal growth factor like factor ( HB EGF ) and betacellulin were significantly higher than those in normal urothelia . ^^^ AG 1478 decreased the expression of genes for amphiregulin , HB EGF and betacellulin , showing that EGFR activation induces up regulation of the EGFR ligands . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Angiotensin 2 ( Ang 2 ) mediated signals are transmitted via heparin binding epidermal growth factor ( EGF ) like growth factor ( HB EGF ) release followed by transactivation of EGF receptor ( EGFR ) . ^^^ Neutralizing anti HB EGF antibody blocked EGFR phosphorylation by Ang 2 . ^^^ Ang 2 also upregulated vascular endothelial growth factor ( VEGF ) expression in an HB EGF / EGFR dependent manner . ^^^ These findings suggested that ( 1 ) Ang 2 induces Ang 2 and VEGF expression without affecting Ang 1 or Tie 2 and ( 2 ) AT ( 1 ) stimulates processing of pro HB EGF by metalloproteinases , and the released HB EGF transactivates EGFR to induce angiogenesis via the combined effect of Ang 2 and VEGF , whereas AT ( 2 ) attenuates them by blocking EGFR phosphorylation . ^^^ Thus , Ang 2 is involved in the VEGF Ang Tie 2 system via HB EGF mediated EGFR transactivation , and this link should be considerable in pathological conditions in which collateral blood flow is required . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
We studied the roles of HB EGF and endothelial growth factor ( EGF ) receptor ( EGFR ) in Ang 2 induced FN expression using mesangial cells . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
CONCLUSION : The expression of EGFR was present in human preimplantation embryos , heparin binding EGF like epidermal growth factor ( HB EGF ) , one of the EGF superfamily members act through the EGFR , EGFR expression may have an important role in human embryos growth , development and implantation . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
We found that the shedding of heparin binding epidermal growth factor ( HB EGF ) resulting from metalloproteinase activation and subsequent transactivation of the epidermal growth factor receptor occurred when cardiomyocytes were stimulated by GPCR agonists , leading to cardiac hypertrophy . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Studies from our laboratory as well as two other groups have demonstrated that EGFR transactivation by different GPCR agonists and in different cell types , including SMCs , is mediated by heparin binding EGF like growth factor ( HB EGF ) . ^^^ HB EGF dependent EGFR activation is blocked by heparin , a growth inhibitor of SMCs in vitro and in vivo . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
PAF R induced transactivation of the EGF R was blocked by pharmacologic inhibitors of matrix metalloproteinases , of heparin binding epidermal growth factor ( HB EGF ) , and specific inhibitors of the EGF R tyrosine kinase . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Structural analysis suggested that SF HB EGF is a secreted polypeptide that has high affinity for heparin , but weakly , if at all , interacts with EGFR . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Furthermore , treatment of SMG rudiments with the hydroxamate based metalloproteinase inhibitor OSU 8 1 , which inhibits processing of EGFR ligands including HB EGF , markedly diminished the growth factor activity in conditioned media and resulted in almost complete inhibition of SMG morphogenesis . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Induction of heparin binding epidermal growth factor like growth factor ( HB EGF ) mRNA in mouse skin organ culture was blocked by two pan ErbB receptor tyrosine kinase ( RTK ) inhibitors but not by genetic ablation of ErbB 1 , suggesting involvement of multiple ErbB species in skin physiology . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
HB EGF induced phosphorylation of the EGF receptor ( EGFR ) with maximum phosphorylation at 0 . 5 to 1 minute , whereas erbB 4 , the other receptor to which HB EGF binds , was not activated on HB EGF stimulation . ^^^ HB EGF induced phosphorylation of these kinases was blocked by the EGFR kinase inhibitor AG 1478 . ^^^ These results demonstrate that HB EGF induced mitogenesis requires both ERK and phosphatidylinositol 3 kinase ( Akt and p70S6K ) pathways activated through EGFR , thereby providing a new mechanistic insight by which HB EGF contributes to vascular remodeling . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Because metalloproteinase mediated cleavage of the HB EGF transmembrane precursor is known to be ERK dependent , our data suggest that ERK activation resulting from initial trauma leads to metalloproteinase mediated cleavage of HB EGF , thereby triggering the ErbB signaling cascade . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
HB EGF ( 5 100 ng / ml ) stimulated by approximately 80 % the incorporation of bromodeoxyuridine ( BrdU ) into cultured cells that expressed the HB EGF receptors epidermal growth factor receptor ( EGFR ) / avian erythroblastic leukemia viral oncogene homolog 1 ( ErbB 1 ) and N arginine dibasic convertase ( NRDc ) . ^^^ Intracerebroventricular administration of HB EGF in adult rats increased BrdU labeling in the subventricular zone and in the subgranular zone of dentate gyrus , where EGFR / ErbB1 and NRDc were also expressed and where ischemia induced neurogenesis is observed . ^^^ We conclude that HB EGF stimulates neurogenesis in proliferative zones of the adult brain that are also affected in ischemia and that it does so by interacting with EGFR / ErbB1 and possibly NRDc . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
This study demonstrates that H . pylori exposure to MKN 1 , ST 42 , and MKN 28 gastric epithelial tumour cells results in the activation of HB EGF gene expression and EGFR tyrosine phosphorylation . ^^^ The induction of HB EGF gene transcription by H . pylori requires metalloprotease , EGFR , and Mek 1 activities , indicating the involvement of the `` triple membrane passing signal ' ' ( TMPS ) for EGFR transactivation . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
The effect of KUZ on shedding of HB EGF and consequent transactivation of the EGFR depends on its metalloprotease activity . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
We further observed that HB EGF induces autophosphorylation of ErbB 1 and ErbB 4 in the uterus and blastocyst . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
CONCLUSIONS : The present study demonstrated that HB EGF processed and released via PC PLC PKC signaling is an intermediate molecule for TGF beta mediated EGFR transactivation , and subsequent activation of ERK and p38MAPK is involved in FN expression via transcriptional regulation without requiring new protein synthesis . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
The IL 6 mediated growth of myeloma cells was also inhibited by antibodies to ErbB 1 , a receptor for HB EGF . ^^^ The XG 1 and XG 14 cell lines that are sensitive to HB EGF inhibitors overexpressed HB EGF and EGF receptor ( ErbB 1 ) genes . ^^^ They also overexpressed CD 9 , a tetraspanin that binds to the heparin binding domain of HB EGF and is critical for promoting ErbB 1 activation by HB EGF . ^^^ The XG 6 and XG 13 myeloma cells that were not significantly sensitive to HB EGF antagonists , poorly expressed HB EGF , ErbB 1 and CD 9 genes or proteins . ^^^ The myeloma cell growth factor activity of HB EGF was completely inhited by antibodies to ErbB 1 , but also by antibodies to gp 130 IL 6 transducer or to IL 6 . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Heparin binding epidermal growth factor like growth factor ( HB EGF ) , a member of the ErbB receptor ligand family , exists in distinct molecular forms with disparate biological activities . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
The mode of activation of EGFR in response to bacterial lipoteichoic acid involves cleavage of the transmembrane ligand HBEGF by ADAM 10 , whereas the activation of EGFR in response to smoke involves cleavage of amphiregulin by ADAM 17 . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
For example , cells expressing TGFalpha and HB EGF will generate protection primarily through EGFR . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Up regulation of transmembrane tyrosine kinase receptors c met , IGFR 1 , IGFR 2 and EGFR family related ligands such as HB EGF , TGFa , amphiregulin and neuregulin as well as c met ligand HGF point to a possible role of this system in metastasis . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Heparin binding epidermal growth factor like growth factor ( HB EGF ) is known to induce cell growth in various cell types via transactivation of epidermal growth factor receptor ( EGFR ) . ^^^ To investigate the involvement of HB EGF and EGFR in cardiac remodeling after myocardial infarction ( MI ) , we examined the expressions of mRNA and protein in rat hearts 6 weeks after MI induction . ^^^ We suggest that the interaction between HB EGF and EGFR transactivation is closely related to the proliferation of cardiac fibroblasts and cardiac remodeling after MI in an autocrine , paracrine , and juxtacrine manner . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
We observed that EGF and HB EGF , but not heregulin , promoted caveolin 1 phosphorylation in A 431 cells , suggesting that these responses are linked to EGF receptor activation and not solely occurring via the activation of other endogenous ErbB family members . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Transactivation / phosphorylation of EGFR by E 2 was dependent on the rapid liberation of heparin binding EGF ( HB EGF ) from cultured MCF 7 cells and was blocked by antibodies to this ligand for EGFR . ^^^ This leads to HB EGF transactivation of EGFR and signaling to multiple kinase cascades in several target cells for E 2 . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
The primary cognate HB EGF receptor , ErbB 1 , has been shown recently to be transactivated by G protein coupled receptors ( GPCRs ) through regulated proteolytic cleavage of the membrane bound , precursor form of HB EGF . ^^^ ErbB 1 and ErbB 2 receptors were activated by HB EGF . ^^^ Furthermore , Ang 2 was able to transactivate both ErbB 1 and ErbB 2 , and this transactivation activity could be abolished by pretreatment with [ Glu 52 ] diphtheria toxin / CRM197 , a specific inhibitor of HB EGF bioactivity . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Heparin binding epidermal growth factor ( HB EGF ) and betacellulin ( BTC ) are activating ligands for EGF receptor ( EGFR / ErbB1 ) and ErbB 4 . ^^^ These results suggest that cardiac valvulogenesis is dependent on EGFR activation by TACE derived soluble HB EGF , and that EGFR signaling is required to regulate bone morphogenetic protein signaling in this context . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
RT PCR transcripts of EGFR ligands ( EGF , TGF alpha , HB EGF , and amphiregulin ) were detected in both carcinomas and normal mucosa , indicating that autocrine growth stimulation of colorectal carcinomas is mediated by coexpression of EGF receptor ligands and upregulation of EGF receptors . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Primary keratinocytes from c jun ( Deltaep ) mice proliferate poorly , show increased differentiation , and form prominent cortical actin bundles , most likely because of decreased expression of EGFR and its ligand HB EGF . ^^^ Thus , using three experimental systems , we show that EGFR and HB EGF are regulated by c Jun , which controls eyelid development , keratinocyte proliferation , and skin tumor formation . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
The heparin binding epidermal growth factor ( EGF ) like growth factor ( HB EGF ) is a member of the EGF family of growth factors that binds to and activates the EGF receptor ( EGFR ) and the related receptor tyrosine kinase , ErbB 4 . ^^^ The cardiac valve and the ventricular chamber phenotypes resembled those displayed by mice lacking EGFR , a receptor for HB EGF , and by mice conditionally lacking ErbB 2 , respectively . ^^^ HB EGF induced tyrosine phosphorylation of ErbB 2 and ErbB 4 , and to a lesser degree , of EGFR in cardiac myocytes . ^^^ HB EGF ErbB interactions in the heart were examined in vivo by administering HB EGF to WT mice . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
We found that the shedding of HB EGF via metalloproteinase activation and subsequent transactivation of the epidermal growth factor receptor occurred when cardiomyocytes were stimulated by GPCR agonists , leading to cardiac hypertrophy . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Of the tested growth factors , heparin binding epidermal growth factor ( HB EGF ) was diffusely expressed throughout normal and psoriatic epidermis and sparsely colocalized with EGFr in all viable epidermal layers , with increased colocalization in psoriatic epidermis . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
The phosphorylation of ERK was reduced by tyrphostin AG 1478 , an inhibitor of phosphorylation of the epidermal growth factor receptor ( EGFR ) , and by heparin , which neutralizes heparin binding epithelial growth factor ( HB EGF ) , suggesting the involvement of a transactivation process , in which alpha ( 2 ) adrenergic stimulation leads to proteolytic shedding of HB EGF ( and perhaps other EGFR agonists ) from transmembrane spanning precursors . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
To test a functional role for HB EGF in ET 1 signaling , we showed that exogenous HB EGF stimulated phosphorylation of ErbB 1 and growth of mesangial cells . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
In undigested , matrix laden fibroblasts , HB EGF significantly downregulates elastin mRNA via activation of epidermal growth factor receptor . ^^^
Interacting proteins: Q99075 and P00533	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 . ^^^ These results suggest an important role for HB EGF and ErbB receptors in the recruitment of SMCs by ECs and elaborate on the mechanism by which angiopoietins exert their vascular effects . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
This regeneration was accompanied by increased HB EGF mRNA expression in cultures of cells from four of six subjects , but no corresponding change in EGFR protein level was observed . ^^^ Our data support an autocrine role of HB EGF in this process and suggest that the EGFR pathway is a potential therapeutic target for modulating urothelial cell proliferation . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
METHODS : RT PCR and indirect immunofluorescence staining for HB EGF and its receptors , such as EGFR and HER4 / erbB4 , were performed on PC 3 cells . ^^^ The influences of bombesin , anti EGFR neutralizing monoclonal antibody , HB EGF , and HB EGF shedding inhibitor on the migration of PC 3 cells were studied by means of in vitro wound assays . ^^^ RESULTS : PC 3 expressed HB EGF and EGFR , but not HER4 / erbB4 . ^^^ In addition , the EGFR on PC 3 was activated in the presence of bombesin and inactivated in the presence of HB EGF shedding inhibitor . ^^^ CONCLUSIONS : These results indicated that HB EGF shedding and the following transactivation of EGFR occurs in this pathway and that this pathway partly contributes to the migration of prostate cancer cells . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
In contrast , phosphorylation of the EGF R , Shc , and ERK1 / 2 by EGF and HB EGF was independent of PKC and metalloprotease activity . ^^^ The signaling characteristics of HB EGF closely resembled those of GnRH and EGF in terms of the phosphorylation of EGF R , Shc , ERK1 / 2 , and RSK 1 as well as the nuclear translocation of RSK 1 . ^^^ These data indicate that the GnRH induced transactivation of the EGF R and the subsequent ERK1 / 2 phosphorylation result from ectodomain shedding of HBEGF through PKC dependent activation of metalloprotease ( s ) in neuronal GT 1 7 cells . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Six of 9 myeloma cell lines and 9 of 9 purified primary myeloma cells expressed ErbB 1 or ErbB 4 genes coding for HB EGF receptor . ^^^ A pan ErbB inhibitor blocked the myeloma cell growth factor activity and the signaling induced by HB EGF . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
We characterized the expression of epidermal growth factor ( EGF ) like growth factors ( EGF , transforming growth factor alpha ( TGF alpha ) , heparin binding EGF like growth factor ( HB EGF ) , betacellulin ( BTC ) , amphiregulin ( APR ) , epiregulin ( EPR ) and neuregulin ( NRG ) 1 ) and erbB receptors ( EGF receptor ( EGFR ) , erbB2 / neu , erbB 3 and erbB 4 ) in the vaginae of mice treated either neonatally ( 0 4 day ) or as adults ( 55 59 day ) with estrogens . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Matrix metalloproteinase ( MMP ) dependent shedding of heparin binding epidermal growth factor ( HB EGF ) and subsequent activation of the EGF receptor ( EGFR ) in the cardiovasculature is emerging as a unique mechanism signaling growth effects of diverse G protein coupled receptors ( GPCRs ) . ^^^ In isolated microperfused arteries , blockade of EGFR transactivation with inhibitors of the EGFR ( AG 1478 and PD 153035 ) , HB EGF ( CRM 197 and neutralizing antibodies ) , or MMPs ( doxycycline ) inhibited adrenergic vasoconstriction . ^^^ These findings suggest a previously unknown mechanism of vasoregulation whereby agonists of certain GPCRs ( such as adrenoceptors and angiotensin receptors ) activate MMPs ( such as MMP 7 ) that shed EGFR ligands ( such as HB EGF ) , which then activate the EGFR , thereby promoting vasoconstriction as well as growth . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
In rat SMCs , thrombin transactivates the epidermal growth factor receptor ( EGFR ) via a pathway that involves heparin binding EGF like growth factor ( HB EGF ) as ligand for EGFR . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Immunocytochemistry on kidney sections using specific antibodies against TGF alpha , HB EGF , EGFr , IGF 1Rbeta , Grb 2 , and phospho p44 / 42 MAP kinase ( ERK1 / 2 ) revealed a significantly higher staining of these molecules 3 to 72 hours after dosing , indicating up regulation of the ERK pathway . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Cleavage of membrane anchored heparin binding EGF like growth factor ( proHB EGF ) via metalloprotease activation yields amino and carboxy terminal regions ( HB EGF and HB EGF C , respectively ) , with HB EGF widely recognized as a key element of epidermal growth factor receptor transactivation in G protein coupled receptor signaling . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
The epidermal growth factor receptor ( EGFR ) and ectoshedding of heparin binding epidermal growth factor ( HBEGF ) , an EGFR ligand , have been linked to the development of cardiac myocyte hypertrophy . ^^^ ET in turn induces metalloproteinase mediated cleavage of pro HBEGF and ectoshedding of HBEGF , which activates the EGFR and stimulates hBNP promoter activity . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Moreover , we report that the EGFR transactivation signal involves the EGFR ligands amphiregulin , HB EGF and TGFalpha as well as the metalloproteinases ADAM 10 , 15 and 17 , depending on the cellular system . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Consistent with its agonist action , HB EGF stimulation of these cells caused marked phosphorylation of the EGF R and its adapter molecule , Shc , as well as ERK1 / 2 and its dependent protein , p 90 ribosomal S 6 kinase , in a manner similar to that elicited by Ang 2 or EGF . ^^^ Although the Tyr 319 residue of the AT 1 R has been proposed to be an essential regulator of EGF R transactivation , stimulation of wild type and mutant ( Y319F ) AT 1 R expressed in COS 7 cells caused EGF R transactivation and subsequent ERK1 / 2 phosphorylation through release of HB EGF in a Src dependent manner . ^^^ These data demonstrate that the individual actions of Ang 2 on EGF R transactivation in specific cell types are related to differential involvement of MMP dependent HB EGF release . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
MATERIALS AND METHODS : We investigated the expression of HB EGF , BTC , EPR and EGF receptor ( EGF R ) in 43 human MFH tissue samples using immunohistochemical techniques . ^^^ RESULTS : Positive immuno reactivity for HB EGF , BTC , EPR and EGF R was identified in 28 ( 65 % ) , 7 ( 16 % ) , 43 ( 100 % ) and 36 ( 84 % ) out of the 43 MFH cases analyzed , respectively . ^^^ Coexpression of HB EGF / EGF R , BTC / EGF R and EPR / EGF R was observed in 25 ( 58 % ) , 6 ( 14 % ) and 36 ( 84 % ) of the MFHs , respectively . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
METHODS : Epithelial monolayers of a telomerase immortalized HCEC line , HUCL , and primary culture of HCECs were infected with Pseudomonas aeruginosa in the presence of the EGFR inhibitor tyrphostin AG 1478 , the extracellular signal regulated kinase ( ERK ) inhibitor U 0126 , the phosphoinositide 3 kinase ( PI3K ) inhibitor LY 294002 , the heparin binding EGF like growth factor ( HB EGF ) antagonist CRM 197 , the HB EGF neutralizing antibody , or the matrix metalloproteinase inhibitor GM 6001 . ^^^ Blocking HB EGF ectodomain shedding by inhibition of matrix metalloproteinase mediated proteolysis , downregulation of HB EGF , or neutralization of its activity retarded infection induced EGFR transactivation and , as a consequence , increased infection induced HUCL apoptosis . ^^^ CONCLUSIONS : Bacterial infection of HCECs induces EGFR transactivation through HB EGF ectodomain shedding . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Stimulation with ufCB also induced processing of membrane anchored proheparin binding ( HB ) EGF , release of soluble HB EGF into the medium , association of phosphorylated EGF R and Shc with glutathione S transferase Grb 2 fusion protein , and phosphorylation of extracellular signal regulated kinase ( ERK ) . ^^^ These results suggest that ufCB causes oxidative stress mediated proliferation of airway epithelium , involving processing of HB EGF and the concomitant activation of EGF R and ERK cascade . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
The mature HB EGF molecule manifests its activity as either a soluble factor ( sol HB EGF ) or a transmembrane precursor ( tm HB EGF ) and can bind two receptors , EGFR and ErbB4 / HER4 . ^^^ In this study , we identify factors that modulate expression of HB EGF , EGFR , and ErbB 4 in endometrial stromal cells in vitro . ^^^ We demonstrate that levels of sol and tm HB EGF , EGFR , and ErbB 4 are increased by cAMP , a potent inducer of decidualization of the endometrial stroma . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
The defects of TGF alpha signaling by excess biglycan were further augmented by the interruption of the autocrine or paracrine loop of the EGFR signaling pathway of HB EGF expression elicited by TGF alpha . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
We found that among the epidermal growth factor receptor ( EGFR ) family of growth factors , HB EGF gene expression in cancerous tissues and HB EGF protein levels in patients ' ascites fluid were significantly elevated . ^^^ LPA , which is constitutively produced by ovarian cancer cells , induced HB EGF ectodomain shedding in SKOV 3 and RMG 1 cells , resulting in the transactivation of EGFR and the downstream kinase extracellular signal regulated kinase / mitogen activated protein kinase . ^^^ Introduction of lipid phosphate phosphohydrolase , which hydrolyzes LPA , decreased the constitutive shedding of HB EGF , EGFR transactivation , and the tumorigenic potential of SKOV 3 and RMG 1 cells . ^^^ These results indicate that HB EGF is the primary member of the EGFR family of growth factors expressed in ovarian cancer and that LPA induced ectodomain shedding of this growth factor is a critical step in tumor formation , making HB EGF a novel therapeutic target for ovarian cancer . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
These data suggest that alpha 1 adrenoceptor mediated SMC growth requires ROS dependent shedding of HB EGF , transactivation of EGFR , and activation of the MEK1 / 2 dependent MAP kinase pathway . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Intriguingly , within myotome pairs , the expression of HB EGF is stronger on the left side of the body , whilst cognate receptors , ErbB 1 and ErbB 4 , are symmetrically expressed in left and right somite pairs . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Stepwise increases in pressure resulted in MT development associated with increased EGFR phosphorylation and release of heparin binding EGF ( HB EGF ) , a membrane bound growth factor that is shed on cleavage by metalloproteinases . ^^^ CONCLUSIONS : These novel findings suggest that the mechanism of pressure induced MT involves metalloproteinases 2 / 9 activation with subsequent HB EGF release and EGFR transactivation . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Effects of erbB 2 depletion on heparin binding EGF like growth factor ( HB EGF ) induced cell migration were determined by Boyden chamber migration assay and by scratch wound assay . ^^^ Depletion of functional erbB 2 attenuated the healing of scratch wounds in the presence of HB EGF and impaired both chemotactic migration stimulated by HB EGF and haptotactic migration toward a fibronectin collagen 1 ( 3 : 1 ; FNC ) coating mix . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
TGF beta 1 is known to transactivate the 170 kDa EGF receptor ( EGFR ) by autocrine HB EGF or TGF alpha mechanisms suggesting involvement of EGFR activation in certain TGF beta 1 initiated responses . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Rat lacrimal gland expressed EGF , TGF alpha , HB EGF , and heregulin mRNA , and all four ErbB receptors were present in the lacrimal gland as detected by western blot analyses . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Neutralizing antibody against HB EGF as a key ligand for EGFR also blocked transactivation of EGFR and cell proliferation by IL 8 . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Western analysis assessed kidney expression of amphiregulin ( AR ) , epidermal growth factor ( EGF ) , heparin binding EGF ( HB EGF ) , and their receptors , EGFR and ErbB 4 . ^^^ AR , EGF , HB EGF , EGFR , and ErbB 4 were abnormally expressed to an equal degree in kidneys of mice with versus without TGF alpha . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Heparin binding epidermal growth factor like growth factor ( HB EGF ) , an ErbB 1 ligand and prostate stromal growth factor , is an antagonist of androgen receptor ( AR ) function . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Proliferation promoting activity in peritoneal fluid from 63 ovarian cancer patients ( OVCA ) was much higher than peritoneal fluid from 18 ovarian cyst patients ( OVC ) and 18 normal ovary patients ( NO ) , and the activity was suppressed only by antibodies against EGFR or heparin binding epidermal growth factor ( HB EGF ) . ^^^ A large difference was observed in the level of EGFR ligands between HB EGF and TGF alpha or amphiregulin . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Ligands containing the HB EGF membrane anchor , but lacking an N terminal extension , activated EGFR during their transit through the Golgi apparatus . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Although the EGFR ligand , heparin binding epidermal growth factor like growth factor ( HB EGF ) , is known to be released as a result of this stimulation , whether compressive stress enhances expression of other EGFR ligands , and the duration of mechanical compression required to initiate this response , is not known . ^^^ Compressive stress produced a sustained upregulation of the EGFR ligands HB EGF , epiregulin , and amphiregulin , but not transforming growth factor alpha . ^^^ Inhibition with AG 1478 demonstrated that expression of HB EGF , epiregulin , and amphiregulin is dependent on the signaling via the EGFR . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
The effect of HB EGF was also blocked by the EGF receptor ( EGFR / ErbB1 ) inhibitors PD 153035 and PD 158780 , implicating EGFR in HB EGF induced cell proliferation . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Pretreatment of NSCLC cells with neutralizing antibodies to the EGFR ligands , TGF A or HB EGF , also decreased GRP mediated MAPK activation . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Treatment of astrocytes with other EGF receptor ( ErbB 1 ) ligands , such as TGF alpha and HB EGF , produced increases in CSPG production similar to those observed with EGF . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
BACKGROUND : The objective of this study was to elucidate gene expression and immunolocalization of heparin binding epidermal growth factor like growth factor ( HB EGF ) and human epidermal growth factor receptor ( HER ) family in the human ovary during luteal growth and regression . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
RESULTS : Large differences in expression were found for heparin binding EGF like growth factor ( HB EGF ) and other EGFR ligands and for ADAM 17 and other ADAM family members . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Among the EGFR ligands , heparin binding EGF like growth factor ( HB EGF ) is a representative ligand to understand the pathophysiological roles of the ectodomain shedding in wound healing , cardiac diseases , etc . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Blocking of ErbB 1 , phosphatidylinositol 3 kinase ( PI3K ) / Akt , or mitogen activated protein kinase / ERK kinase ( MEK ) / ERK activity resulted in significant reduction in intrinsic and HB EGF induced restitution in vitro . ^^^ Endogenous HB EGF was shown to play an essential role in wound induced ErbB 1 and ERK1 / 2 activation and in intrinsic restitution . ^^^ CONCLUSIONS : Endogenous HB EGF , ErbB 1 , PI3K / Akt , and MEK / ERK are involved in intrinsic restitution . rHB EGF enhances restitution in vivo and in vitro in a PI3K / Akt and MEK / ERK1 / 2 dependent fashion . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
A G protein coupled receptor agonist , angiotensin 2 ( AngII ) , induces epidermal growth factor ( EGF ) receptor ( EGFR ) transactivation possibly through metalloprotease dependent , heparin binding EGF ( HB EGF ) shedding . ^^^ In these cells AngII induced EGFR transactivation was completely inhibited by pretreatment with a selective HB EGF inhibitor , or with a metalloprotease inhibitor . ^^^ Moreover , infection of an adenovirus encoding an inhibitor of G ( q ) markedly reduced EGFR transactivation and HB EGF shedding through AT 1 . ^^^ From these data we conclude that AngII stimulates a metalloprotease ADAM 17 dependent HB EGF shedding through AT1 / G ( q ) / phospholipase C mediated elevation of intracellular Ca2+ and reactive oxygen species production , representing a key mechanism indispensable for EGFR transactivation . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Using two site enzyme immunoassays , we measured protein levels of epidermal growth factor ( EGF ) , transforming growth factor alpha ( TGF alpha ) , and heparin binding epidermal growth factor ( HB EGF ) in adult rat brain , and compared them with the phosphorylation levels of their receptor ( ErbB 1 ) . ^^^ Among these ErbB 1 ligands , HB EGF protein levels were higher than those of TGF alpha and those of EGF were the lowest . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Heparin binding EGF like growth factor ( HB EGF ) is a member of the EGF family of growth factors that binds to and activates the EGF receptor ( EGFR ) and ERBB 4 . ^^^ Here , we show that HB EGF EGFR signaling is involved in eyelid development . ^^^ Crosses between HB ( del / del ) mice and waved 2 mice , a hypomorphic EGFR mutant strain , indicate that HB EGF and EGFR interact genetically in eyelid closure . ^^^ Together with our data showing that embryos treated with an EGFR specific kinase inhibitor phenocopy HB ( del / del ) embryos , these data indicate that EGFR mediates HB EGF dependent eyelid closure . ^^^ These results indicate that soluble HB EGF secreted from the tip of the leading edge activates the EGFR and ERK pathway , and that synergy with TGFalpha is required for leading edge extension in epithelial sheet migration during eyelid closure . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
A literature search was undertaken using PubMed and MEDLINE search engines , using the keywords p 53 , p 21 , p 16 , p 27 , SMAD 4 , K ras , cyclin D 1 , Bax , Bcl 2 , EGFR , EGF , c erbB 2 , HB EGF , TGFbeta , FGF , MMP , uPA , cathepsin , heparanase , E cadherin , laminins , integrins , TMSF , CD 44 , cytokines , angiogenesis , VEGF , IL 8 , beta catenin , DNA microarray , and gene profiling . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Plasmin can also activate metalloproteinases on the cell surface , which can release the tethered ligand heparin binding epidermal growth factor ( HB EGF ) , which can in turn activate the epidermal growth factor receptor ( EGFR ) . ^^^ Assays of DNA synthesis and cell proliferation , EGFR phosphorylation , and ERK1 / 2 activation were examined in response to plasmin in the presence and absence of the plasmin inhibitors ( epsilon aminocaproic acid and aprotinin ) , matrix metalloproteinase ( MMP ) inhibitor GM 6001 , HB EGF inhibitor CRM 197 , HB EGF inhibitory antibodies , EGF inhibitory antibodies , and the EGFR inhibitor AG 1478 . ^^^ RESULTS : Plasmin induced smooth muscle cell DNA synthesis , which was blocked by EGFR and HB EGF inhibition . ^^^ EGFR phosphorylation by plasmin was blocked by inhibition of MMP activity and the ligand HB EGF . ^^^ EGFR phosphorylation by EGF was not interrupted by inhibition of plasmin , MMPs , or HB EGF . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Production of ROS resulted in EGF receptor ( EGFR ) and Akt 1 phosphorylation in HB EGF expressing cells . ^^^
Interacting proteins: Q99075 and P00533	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: Q99075 and P00533	Pubmed	SVM Score :0.0
Topical tRA activates extracellular signal regulated kinase 1 / 2 ( Erk1 / 2 ) downstream EGFR effectors in human skin in vivo . tRA increases the soluble forms of AR and HB EGF proteins , and induces epidermal hyperplasia , in human skin organ culture . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
We hypothesize that Ang 2 promotes the proliferation and migration of smooth muscle cells through the release of heparin binding epidermal growth factor like growth factor ( HB EGF ) , transactivation of EGFR and activation of Akt and Erk 1 / 2 , with matrix metalloproteases ( MMPs ) playing a dispensable role . ^^^ Furthermore Ang 2 stimulated proliferation and migration of smooth muscle cells were significantly blunted by inhibiting MMPs and EGFR and applying HB EGF neutralization antibody , indicating that MMPs , HB EGF and EGFR activation is necessary for Ang 2 stimulated migration and proliferation of smooth muscle cells . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Phe induced phosphorylation of the EGF R , and subsequently of Shc and ERK1 / 2 , was attenuated by inhibition of MMP or HB EGF with the selective inhibitor , CRM 197 , or by a neutralizing antibody . ^^^ In contrast , phosphorylation of the EGF R , Shc and ERK1 / 2 by EGF and HB EGF was independent of PKC and MMP activity . ^^^ Moreover , inhibition of Src attenuated ERK1 / 2 responses by Phe , but not by HB EGF and EGF , indicating that Src acts upstream of the EGF R . ^^^ These data suggest that activation of the alpha 1 AR causes phosphorylation of ERK1 / 2 through activation of PKC , ROS and Src , and shedding of HB EGF , which binds to and activates the EGF R . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Transactivation of epidermal growth factor receptor ( EGFR ) by G protein coupled receptors ( GPCRs ) has been attributed to the activation of matrix metalloproteases ( MMPs ) and the release of EGF family ligands such as HB EGF . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Among ErbB tyrosine kinase receptors , EGF receptor ( EGFR ) and ErbB 2 were selectively activated by tRA treatment in skin from wild type mice , while the activation of these ErbB receptors was significantly reduced in the skin of HB EGF null mice . ^^^ These results indicate that expression of HB EGF and generation of its soluble form , followed by activation of EGFR and ErbB 2 , are pivotal processes in tRA induced epidermal hyperplasia . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Expression of wild type EGFR ligands , such as transforming growth factor alpha ( TGF alpha ) or heparin binding EGF ( HB EGF ) , is also often increased in gliomas resulting in an autocrine loop that contributes to the growth autonomy of glioma cells . ^^^ The mutant receptor does not bind ligand , and EGFRvIII induced expression of TGF alpha and HB EGF suggests that EGFRvIII plays a role in generating an autocrine loop using the wild type EGFR in glioma . ^^^ This suggests that the EGFRvIII HB EGF wild type EGFR autocrine loop plays an important role in signal transduction by EGFRvIII in glioma cells . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
The heparin binding EGF like growth factor ( HB EGF ) is a member of the EGF family of growth factors that binds to and activates the EGF receptor ( EGFR / ErbB1 ) and ErbB 4 . ^^^ HB EGF signaling through ErbB 2 is essential for the maintenance of homeostasis in the adult heart , whereas HB EGF signaling through EGFR is required during cardiac valve development . ^^^ ErbB and HB EGF signaling in heart development and function . ^^^ Recent studies using several mutant mice lacking HB EGF expression have revealed that HB EGF has a critical role in normal heart function and in normal cardiac valve formation in conjunction with ErbB receptors . ^^^ In this review , we introduce and discuss the role of ErbB receptors in heart function and development , focusing on the physiological function of HB EGF in these processes . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
It has been reported that G protein coupled receptor ( GPCR ) activation induces epidermal growth factor ( EGF ) receptor ( EGFR ) transactivation through the shedding of heparin binding EGF like growth factor ( HB EGF ) . ^^^ Ang 2 induced EGFR phosphorylation , which was inhibited by an AT1R antagonist , HB EGF neutralizing antibody , and an HB EGF antagonist in both keratinocytes and in fibroblasts . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
BACKGROUND / AIMS : Activation of angiotensin 2 ( ANG 2 ) receptors stimulates extracellular signal regulated kinases ( ERKs ) that , in some cell systems , are mediated by transactivating the epidermal growth factor ( EGF ) receptor ( EGFR ) through mechanisms involving matrix metalloprotease ( MMP ) stimulated processing of heparin binding EGF ( HB EGF ) from its precursor . ^^^ ANG 2 dependent ERK activation was inhibited by : ( 1 ) the type 1 ANG 2 selective antagonist losartan ; ( 2 ) the type 2 ANG 2 selective antagonist PD 123319 ; ( 3 ) an inhibitor of MMP2 / 9 ; ( 4 ) the EGFR kinase inhibitor AG 1478 , and ( 5 ) the HB EGF antagonists CRM 197 and heparin . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
HB EGF , a member of the EGF family of growth factors , exerts its biological activity through activation of the EGFR and other ErbB receptors . ^^^ Recent studies have indicated that HB EGF gene expression is significantly elevated in many human cancers and its expression level in a number of cancer derived cell lines is much higher than those of other EGFR ligands . ^^^ HB EGF participates in diverse biological processes , including heart development and maintenance , skin wound healing , eyelid formation , blastocyst implantation , progression of atherosclerosis and tumor formation , through the activation of signaling molecules downstream of ErbB receptors and interactions with molecules associated with HB EGF . ^^^ These results indicate that HB EGF is a promising target for cancer therapy , and that the development of targeting tools against HB EGF could represent a novel type of therapeutic strategy , as an alternative to targeting ErbB receptors . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
AREG ( Amphiregulin ) , BTC ( beta cellulin ) , EGF , EPGN ( Epigen ) , EREG ( Epiregulin ) , HBEGF , NRG 1 , NRG 2 , NRG 3 , NRG 4 and TGFA ( TGFalpha ) constitute EGF family ligands for ERBB family receptors . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
METHODS : SV 40 immortalized HCEC ( THCE ) monolayer was wounded and allowed to heal in the presence or absence of a selective inhibitor of the Src family kinases PP 2 and EGFR ligand heparin binding EGF like growth factor ( HB EGF ) . ^^^ Consistent with the inhibition of EGFR transactivation , PP 2 also attenuated epithelial migration and wound closure with or without exogenously added HB EGF . ^^^ On the other hand , AKT phosphorylation was much more sensitive to PP 2 than ERK or EGFR phosphorylation because 3 . 13 microM PP 2 effectively inhibited wound or HB EGF induced AKT phosphorylation . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
In the present study , we show that keratinocyte migration induced by TGF beta 1 , KGF , EGF , TGF alpha and staurosporine depends on EGFR signaling , involves autocrine HB EGF expression and is potently blocked by GSK 3 inhibitors SB 415286 and LiCl . ^^^ Thus , induction of keratinocyte migration is conveyed through EGFR , promoted by endogenous HB EGF and requires GSK 3alpha activity . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
TbetaT FH expresses high levels of transforming growth factor alpha ( TGF alpha ) and heparin binding EGF like growth factor ( HB EGF ) and shows constitutive activation of the EGFR pathway . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
BACKGROUND : Angiotensin 2 ( Ang 2 ) promotes growth of vascular smooth muscle cells ( VSMCs ) via epidermal growth factor ( EGF ) receptor ( EGFR ) transactivation mediated through a metalloprotease dependent shedding of heparin binding EGF like growth factor ( HB EGF ) . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Treatment of HBEpCs with LPA stimulated tyrosine phosphorylation of EGFR , which was attenuated by matrix metalloproteinase ( MMP ) inhibitor ( GM 6001 ) , heparin binding ( HB ) EGF inhibitor ( CRM 197 ) , and HB EGF neutralizing antibody . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
In this study , we present multiple lines of evidence to support a critical role for heparin bound EGF ( epidermal growth factor ) like growth factor ( HB EGF ) and tumor necrosis factor alpha converting enzyme ( TACE ) ( ADAM 17 ) in the transactivation of EGF receptor ( EGFR ) , ERK phosphorylation , and cellular proliferation induced by the 5 HT ( 2A ) receptor in renal mesangial cells . 5 hydroxy tryptamine ( 5 HT ) resulted in rapid activation of TACE , HB EGF shedding , EGFR activation , ERK phosphorylation , and longer term increases in DNA content in mesangial cells . ^^^ ERK phosphorylation was attenuated by 1 ) neutralizing EGFR antibodies and the EGFR kinase inhibitor , AG 1478 , 2 ) neutralizing HB EGF , but not amphiregulin , antibodies , heparin , or CM 197 , and 3 ) pharmacological inhibitors of matrix degrading metalloproteinases or TACE small interfering RNA . ^^^ In aggregate , this work supports a pathway map that can be depicted as follows : 5 HT > 5 HT ( 2A ) receptor > TACE > HB EGF shedding > EGFR > ERK > increased DNA content . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Based on these data , we propose a model whereby activation of MAPK by alpha ( 2B ) AR is mediated through stimulation of PLA 2 , AA release , generation of AA derivatives , activation of matrix metalloproteinases , release of heparin binding EGF like growth factor , transactivation of epidermal growth factor receptor , and recruitment of Shc . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
In contrast to wild type EGFR ligands , a mutant form of heparin binding EGF like growth factor ( HB 2 ) did not induce dimerization of the EGFR EpoR chimeric receptor and therefore failed to activate the chimeric receptor . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
AngII and other G protein coupled receptor ligands known to transactivate EGFR phosphorylated the 170 kDa EGFR but not the 145 kDa EGFR , whereas EGF , heparin binding EGF like growth factor , and transforming growth factor alpha phosphorylated both receptors . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Blocking Abs against the EGFR or against heparin binding EGF like growth factor similarly blocked IL 8 mediated cell migration and in vitro tubulogenesis in HMECs . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
The present study used isolated arteries and VSMCs to investigate the role of the EGFR ligand heparin binding epidermal growth factor ( HB EGF ) in ET 1 induced transactivation of EGFR , intracellular calcium mobilization , and VSMCs contraction . ^^^ In isolated mouse carotid artery segments mounted in an arteriograph , ET 1 caused only a weak increase in isovolumetric tone in HB EGF deficient vessels , and this effect was mimicked by inhibition of EGFR tyrosine kinase or phosphoinositide 3 kinase ( PI3K ) in wild type arteries with or without endothelium , indicating a specific role in VSMCs . ^^^ EGFR or PI3K inhibitors had no effect on KCl induced contraction , which was normal in HB EGF deficient mice . ^^^ To confirm that the abnormal responses in HB EGF deficient mice were due to impaired EGFR signaling , we studied VSMCs from waved 2 ( wa 2 ) mice ; these animals have a mutation causing a partial loss of function of EGFR tyrosine kinase activity . ^^^ Mutated DT toxin ( CRM 197 ) is devoid of toxicity but it neutralizes HB EGF binding to EGFR . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
There was concomitant phosphorylation of EGF receptors ( ErbB 1 ) following seizures , suggesting that seizure activities liberated HB EGF and activated neighboring ErbB 1 receptors . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
RPE cells express mRNAs for various members of the EGF related growth factor family , among them for HB EGF , as well as for the EGF receptors ErbB 1 , 2 , 3 , and 4 . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Human epidermal growth factor receptor 4 ( HER 4 ) is a member of the epidermal growth factor ( EGF ) receptor subfamily of receptor tyrosine kinases that is activated by neuregulins ( NRG ) , betacellulin ( BTC ) , and heparin binding EGF like growth factor . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Apoptosis induced by PI3K inhibition was attenuated by : ( a ) dihydrotestosterone ; or ( b ) the ErbB 1 activating ligands [ epidermal growth factor ( EGF ) , transforming growth factor alpha , or heparin binding EGF like growth factor ] . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
The products of five distinct loci , Egf , Tgfa , Areg , Btc , and Hegfl act as ligands for the epidermal growth factor receptor . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
In the experiments described here using AGS gastric cancer cells , SN 38 ( the active metabolite of CPT 11 ) induced tyrosine phosphorylation of EGFR within 5 min , and this was followed by the induction of transcripts and / or proteins of heparin binding EGF like growth factor , amphiregulin , transforming growth factor alpha , and interlukin 8 ( IL 8 ) . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
The findings reported here demonstrate that SN 38 ( the active metabolite of CPT 11 ) induces the tyrosine phosphorylation of EGFR within 5 min , followed by the induction of transcripts and / or proteins of the heparin binding EGF like growth factor , amphiregulin , transforming growth factor alpha , and interlukin 8 ( IL 8 ) in AGS gastric cancer cells . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Our results provide evidence for a putative pathway by which alpha ( 2 ) ARs activate MAPK and Akt in PC 12 cells , involving stimulation of PLC , AA release , AA metabolism by cytochrome P 450 dependent epoxygenase , stimulation of matrix metalloproteinases and subtype specific transactivation of EGFR through src activation and heparin binding EGF like growth factor release . . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Hyperproliferative ACF had significantly increased mRNA levels of EGFR ( 6 . 0 + / 1 . 7 fold ) , transforming growth factor alpha ( 14 . 4 + / 5 . 0 fold ) , heparin binding EGF like growth factor ( 4 . 5 + / 1 . 4 fold ) , cyclin D 1 ( 4 . 6 + / 0 . 7 fold ) , and cyclooxygenase 2 ( COX 2 ; 9 . 3 + / 4 . 2 fold ; P < 0 . 05 ) . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
Moreover , using vessels from EGFR ligand deficient mice , we show that transforming growth factor ( TGF ) alpha , but neither heparin binding EGF like growth factor nor epiregulin , transduces NF kappaB activation by high pressure . ^^^
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q99075 and P00533	Pubmed	SVM Score :0.0
NA