1995
DOI: 10.1128/mcb.15.10.5770
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The Cellular Response to Neuregulins Is Governed by Complex Interactions of the erbB Receptor Family

Abstract: Deregulated signaling by the four members of the epidermal growth factor receptor tyrosine kinase family (erbB family) is implicated in the genesis or progression of human cancers. However, efforts to analyze signaling by these receptors have been hampered by the diversity of ligands and extensive interreceptor cross talk. We have expressed the four human erbB family receptors, singly and in pairwise combinations, in a pro-B-lymphocyte cell line (Ba/F3) and investigated the range of interactions activated by t… Show more

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Cited by 366 publications
(384 citation statements)
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“…Epiregulin exhibited a pattern of receptor binding and activation that was di erent from these peptides. Recent reports described the ability of BTC to induce tyrosine phosphorylation of all four ErbB receptors and a possible direct binding to ErbB-4 as well as EGFR (Beerli and Hynes, 1996;Riese et al, 1996a). Although similar receptor binding pro®les were observed, epiregulin is probably di erent from BTC with regard to the magnitude of activation of tyrosine phosphorylation of the four ErbB family receptors.…”
Section: Discussionmentioning
confidence: 86%
See 1 more Smart Citation
“…Epiregulin exhibited a pattern of receptor binding and activation that was di erent from these peptides. Recent reports described the ability of BTC to induce tyrosine phosphorylation of all four ErbB receptors and a possible direct binding to ErbB-4 as well as EGFR (Beerli and Hynes, 1996;Riese et al, 1996a). Although similar receptor binding pro®les were observed, epiregulin is probably di erent from BTC with regard to the magnitude of activation of tyrosine phosphorylation of the four ErbB family receptors.…”
Section: Discussionmentioning
confidence: 86%
“…Notably, a recent report shows that BTC activates EGFR and ErbB-4 in the absence of additional ErbB family receptor expression (Riese et al, 1996a). The other group, neuregulins, is comprised of alternative spliced isoforms from a single gene.…”
Section: Introductionmentioning
confidence: 99%
“…Ba/F3 cells lack endogenous EGFR, ErbB2 and ErbB4 [although ErbB3 is detectable by reverse transcription-polymerase chain reaction (RT-PCR) (Riese et al, 1995)], allowing us to focus on the signaling properties of EGFR itself, without complications from heterodimerization with other ErbB family members. Selected Ba/F3 cell transfectants were sorted using fluorescence-activated cell sorting (FACS) into pools that express matched (within B2-fold) levels of the EGFR variants at the cellsurface (Figure 2).…”
Section: Resultsmentioning
confidence: 99%
“…Signal transduction through type 1 receptor tyrosine kinases is initiated by ligand-induced stabilisation of receptor dimers followed by receptor autophosphorylation and recruitment of speci®c signalling proteins containing Src homology 2 (SH2) domains. Speci®c sets of SH2-containing proteins associate with di erent receptor dimers, thereby giving rise to a broad spectrum of downstream signalling events Riese et al, 1995).…”
Section: Introductionmentioning
confidence: 99%
“…No ligand has yet been identi®ed which binds directly to c-erbB2. Both c-erbB3 and c-erbB4 bind a range of ligands of which the splice variants of neuregulin (heregulin, neu di erentiation factor) have received particular attention (Riese et al, 1995). Despite the absence of a direct ligand, transphosphorylation of c-erbB2 can be induced following heterodimerisation to ligand-bound c-erbB3 or c-erbB4 (Tzahar et al, 1996).…”
Section: Introductionmentioning
confidence: 99%