ARIA, a protein that stimulates acetylcholine receptor synthesis, is a member of the neu ligand family

Falls, Douglas L.; Rosen, Kenneth M.; Corfas, Gabriel; Lane, William S.; Fischbach, Gerald D.

doi:10.1016/0092-8674(93)90407-h

Cited by 573 publications

(397 citation statements)

References 50 publications

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“…EGF [7,8], transforming growth factor-α (TGF-α) [9,10], and amphiregulin [11] uniquely bind EGFR. ErbB3 binds neuregulin-1 [12][13][14][15][16] and neuregulin-2 [17][18][19][20] and uniquely binds Neuroglycan C [21]. ErbB4 is also able to bind neuregulin-1 and neuregulin-2 and uniquely binds neuregulin-3 [22], neuregulin-4 [23], and tomoregulin [24] as well.…”

Section: Receptor Overviewmentioning

confidence: 99%

The epidermal growth factor receptor family: Biology driving targeted therapeutics

Wieduwilt

Moasser

2008

Cell. Mol. Life Sci.

647

503

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The epidermal growth factor family of receptor tyrosine kinases (ErbBs) plays essential roles in regulating cell proliferation, survival, differentiation and migration. The ErbB receptors carry out both redundant and restricted functions in mammalian development and in the maintenance of tissues in the adult mammal. Loss of regulation of the ErbB receptors underlies many human diseases, most notably cancer. Our understanding of the function and complex regulation of these receptors has fueled the development of targeted therapeutic agents for human malignancies in the last 15 years. Here we review the biology of ErbB receptors, including their structure, signaling, regulation, and roles in development and disease, then briefly touch on their increasing roles as targets for cancer therapy.

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Section: Receptor Overviewmentioning

confidence: 99%

The epidermal growth factor receptor family: Biology driving targeted therapeutics

Wieduwilt

Moasser

2008

Cell. Mol. Life Sci.

647

503

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“…In addition, the in vivo role of heregulins as growth-stimulatory factors (GFs) is further suggested by reports of the cloning of genes encoding GFs with almost complete identity to HRG/NDF. These two molecules, acetylcholine receptor-inducing activity or ARIA Falls et al, 1993), and glial growth factor or GGF (Marchionni et al, 1993), activate phosphorylation of p185 HER-2/neu and promote mitogenesis in cells of the peripheral nervous system. More recent data shows that GGF rescues peripheral nervous system cells from various apoptosis-induced conditions (Kopp et al, 1997;Raabe et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Biologic effects of heregulin/neu differentiation factor on normal and malignant human breast and ovarian epithelial cells

Akita²,

et al. 1999

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The heregulins are a family of ligands with ability to induce phosphorylation of the p185 HER-2/neu receptor. Various investigators have reported a variety of responses of mouse and human breast and ovarian cells to this family of ligands including growth stimulation, growth inhibition, apoptosis and induction of di erentiation in cells expressing the HER-2/neu receptor. Some of the disparity in the literature has been attributed to variations in the cell lines studied, ligand dose applied, methodologies utilized or model system evaluated (i.e. in vitro or in vivo). To evaluate the e ects of heregulin on normal and malignant human breast and ovarian epithelial cells expressing known levels of the HER-2/ neu receptor, this report presents the use of several di erent assays, performed both in vitro and in vivo, in vitro proliferation assays, direct cell counts, clonogenicity under anchorage-dependent and anchorage-independent conditions, as well as the in vivo e ects of heregulin on human cells growing in nude mice to address heregulin activity. Using a total of ®ve di erent biologic assays in nine di erent cell lines, across two di erent epithelia and over a one log heregulin dose range, we obtained results that clearly indicate a growth-stimulatory role for this ligand in human breast and ovarian epithelial cells. We ®nd no evidence that heregulin has any growth-inhibitory e ects in human epithelial cells. We also quantitated the amount of each member of the type I receptor tyrosine kinase family (RTK I, i.e. HER-1, HER-2, HER-3 and HER-4) in the cell lines employed and correlated this to their respective heregulin responses. These data demonstrate that HER-2/neu overexpression itself a ects the expression of other RTK I members and that cells expressing the highest levels of HER-2/neu have the greatest response to HRG.

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“…The other group, neuregulins, is comprised of alternative spliced isoforms from a single gene. The group includes neu di erentiation factor (NDF) (Wen et al, 1992)/heregulin (HRG) (Homes et al, 1992), acetylcholine receptor-inducing activity (Falls et al, 1993) and glial growth factor (Marchionni et al, 1993). These ligands do not interact directly with EGFR and ErbB-2 but bind with low a nity to ErbB-3 and high a nity to ErbB-4 (Plowman et al, 1993b;.…”

Section: Introductionmentioning

confidence: 99%

Epiregulin binds to epidermal growth factor receptor and ErbB-4 and induces tryosine phosphorylation of epidermal growth factor receptor, ErbB-2, ErbB-3 and ErbB-4

et al. 1997

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Epiregulin is a member of the epidermal growth factor (EGF) family, and has certain characteristics that are di erent from that of EGF, including mitogenic responses and binding to EGF receptor (EGFR). Epiregulin may also have another cell surface receptor and/or induces di erent receptor heterodimerizations for intracellular signaling. We investigated the binding ability of epiregulin to four ErbB family receptors using four human breast carcinoma cell lines that expressed di erent subsets of receptors. Chemical cross-linking experiments showed that [ 125 I]epiregulin directly bound to each of EGFR and ErbB-4 but not to ErbB-2 and ErbB-3. Furthermore, although epiregulin stimulated tyrosine phosphorylation of all four ErbB receptors, the main intracellular signal was mediated by ErbB-4 and/or EGFR. The pattern of activation of ErbB family receptors was di erent from that of other EGF-related ligands. Our ®ndings indicate that ErbB-4 and EGFR are receptors for epiregulin, and suggest that EGFrelated ligands transduce signals for di erent biological responses by the hierarchical mechanism.

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ARIA, a protein that stimulates acetylcholine receptor synthesis, is a member of the neu ligand family

Cited by 573 publications

References 50 publications

The epidermal growth factor receptor family: Biology driving targeted therapeutics

The epidermal growth factor receptor family: Biology driving targeted therapeutics

Biologic effects of heregulin/neu differentiation factor on normal and malignant human breast and ovarian epithelial cells

Epiregulin binds to epidermal growth factor receptor and ErbB-4 and induces tryosine phosphorylation of epidermal growth factor receptor, ErbB-2, ErbB-3 and ErbB-4

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