Neuregulin-3 (NRG3): A Novel Neural Tissue-Enriched Protein that Binds and Activates ErbB4
We describe the identification of Neuregulin-3 (NRG3), a novel protein that is structurally related to the neuregulins (NRG1). The NRG1/neuregulins are a diverse family of proteins that arise by alternative splicing from a single gene. These proteins play an important role in controlling the growth...
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| Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 94; no. 18; pp. 9562 - 9567 |
|---|---|
| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
National Academy of Sciences of the United States of America
02.09.1997
National Acad Sciences National Academy of Sciences The National Academy of Sciences of the USA |
| Subjects | |
| Online Access | Get full text |
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| Abstract | We describe the identification of Neuregulin-3 (NRG3), a novel protein that is structurally related to the neuregulins (NRG1). The NRG1/neuregulins are a diverse family of proteins that arise by alternative splicing from a single gene. These proteins play an important role in controlling the growth and differentiation of glial, epithelial, and muscle cells. The biological effects of NRG1 are mediated by receptor tyrosine kinases ErbB2, ErbB3, and ErbB4. However, genetic studies have suggested that the activity of ErbB4 may also be regulated in the central nervous system by a ligand distinct from NRG1. NRG3 is predicted to contain an extracellular domain with an epidermal growth factor (EGF) motif, a transmembrane domain, and a large cytoplasmic domain. We show that the EGF-like domain of NRG3 binds to the extracellular domain of ErbB4 in vitro. Moreover, NRG3 binds to ErbB4 expressed on cells and stimulates tyrosine phosphorylation of this receptor. The expression of NRG3 is highly restricted to the developing and adult nervous system. These data suggest that NRG3 is a novel, neural-enriched ligand for ErbB4. |
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| AbstractList | We describe the identification of Neuregulin-3 (NRG3), a novel protein that is structurally related to the neuregulins (NRG1). The NRG1/neuregulins are a diverse family of proteins that arise by alternative splicing from a single gene. These proteins play an important role in controlling the growth and differentiation of glial, epithelial, and muscle cells. The biological effects of NRG1 are mediated by receptor tyrosine kinases ErbB2, ErbB3, and ErbB4. However, genetic studies have suggested that the activity of ErbB4 may also be regulated in the central nervous system by a ligand distinct from NRG1. NRG3 is predicted to contain an extracellular domain with an epidermal growth factor (EGF) motif, a transmembrane domain, and a large cytoplasmic domain. We show that the EGF-like domain of NRG3 binds to the extracellular domain of ErbB4 in vitro. Moreover, NRG3 binds to ErbB4 expressed on cells and stimulates tyrosine phosphorylation of this receptor. The expression of NRG3 is highly restricted to the developing and adult nervous system. These data suggest that NRG3 is a novel, neural-enriched ligand for ErbB4. We describe the identification of Neuregulin-3 (NRG3), a novel protein that is structurally related to the neuregulins (NRG1). The NRG1/neuregulins are a diverse family of proteins that arise by alternative splicing from a single gene. These proteins play an important role in controlling the growth and differentiation of glial, epithelial, and muscle cells. The biological effects of NRG1 are mediated by receptor tyrosine kinases ErbB2, ErbB3, and ErbB4. However, genetic studies have suggested that the activity of ErbB4 may also be regulated in the central nervous system by a ligand distinct from NRG1. NRG3 is predicted to contain an extracellular domain with an epidermal growth factor (EGF) motif, a transmembrane domain, and a large cytoplasmic domain. We show that the EGF-like domain of NRG3 binds to the extracellular domain of ErbB4 in vitro . Moreover, NRG3 binds to ErbB4 expressed on cells and stimulates tyrosine phosphorylation of this receptor. The expression of NRG3 is highly restricted to the developing and adult nervous system. These data suggest that NRG3 is a novel, neural-enriched ligand for ErbB4. Zhang et al describe the identification of Neuregulin-3, a novel protein that is structurally related to the neuregulins. |
| Author | Godowski, Paul J. Sliwkowski, Mark X. Crowley, Craig Zhang, Dongxiao Frantz, Gretchen Mark, Melanie Akita, Robert Sun, Yang Brush, Jennifer Hillan, Kenneth |
| AuthorAffiliation | Departments of Molecular Biology, † Protein Chemistry, and ‡ Pathology, Genentech, Inc., South San Francisco, CA 94080 |
| AuthorAffiliation_xml | – name: Departments of Molecular Biology, † Protein Chemistry, and ‡ Pathology, Genentech, Inc., South San Francisco, CA 94080 |
| Author_xml | – sequence: 1 givenname: Dongxiao surname: Zhang fullname: Zhang, Dongxiao – sequence: 2 givenname: Mark X. surname: Sliwkowski fullname: Sliwkowski, Mark X. – sequence: 3 givenname: Melanie surname: Mark fullname: Mark, Melanie – sequence: 4 givenname: Gretchen surname: Frantz fullname: Frantz, Gretchen – sequence: 5 givenname: Robert surname: Akita fullname: Akita, Robert – sequence: 6 givenname: Yang surname: Sun fullname: Sun, Yang – sequence: 7 givenname: Kenneth surname: Hillan fullname: Hillan, Kenneth – sequence: 8 givenname: Craig surname: Crowley fullname: Crowley, Craig – sequence: 9 givenname: Jennifer surname: Brush fullname: Brush, Jennifer – sequence: 10 givenname: Paul J. surname: Godowski fullname: Godowski, Paul J. |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/9275162$$D View this record in MEDLINE/PubMed |
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| Notes | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 Communicated by David V. Goeddel, Tularik, Inc., South San Francisco, CA To whom reprint requests should be addressed at: Department of Molecular Biology, Mailstop 37, Genentech, Inc., 460 Point San Bruno Boulevard, South San Francisco, CA 94080. e-mail: ski@gene.com. |
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| Snippet | We describe the identification of Neuregulin-3 (NRG3), a novel protein that is structurally related to the neuregulins (NRG1). The NRG1/neuregulins are a... Zhang et al describe the identification of Neuregulin-3, a novel protein that is structurally related to the neuregulins. We describe the identification of Neuregulin-3 (NRG3), a novel protein that is structurally related to the neuregulins (NRG1). The NRG1 /neuregulins are a... |
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| SubjectTerms | Amino Acid Sequence Amino acids Animals Antibodies Biochemistry Biological Sciences Carrier Proteins - genetics Carrier Proteins - metabolism Cell Line Cell lines Cloning, Molecular Complementary DNA Enzyme Activation ErbB Receptors - genetics ErbB Receptors - metabolism Gene Expression Regulation, Developmental Humans Intracellular Signaling Peptides and Proteins K562 cells Ligands Mice Molecular Sequence Data Nerve Growth Factors - genetics Nerve Growth Factors - metabolism Neuregulins Neurons Organ Specificity Phosphorylation Proteins Receptor, ErbB-4 Receptors |
| Title | Neuregulin-3 (NRG3): A Novel Neural Tissue-Enriched Protein that Binds and Activates ErbB4 |
| URI | https://www.jstor.org/stable/43063 http://www.pnas.org/content/94/18/9562.abstract https://www.ncbi.nlm.nih.gov/pubmed/9275162 https://www.proquest.com/docview/201294978 https://search.proquest.com/docview/16241852 https://search.proquest.com/docview/79237371 https://pubmed.ncbi.nlm.nih.gov/PMC23218 |
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