Abstract
The neuregulins (NRGs) are a family of multipotent epidermal-growth-factor-like (EGF-like) factors that arise from splice variants of a single gene. They influence the growth, differentiation, survival and fate of several cell types. We have now discovered a set of new neuregulin-like growth factors, which we call neuregulin-2 (NRG-2): these are encoded by their own gene and exhibit a distinct expression pattern in adult brain and developing heart. Like NRG-1, the EGF-like domain of the new ligands binds to both the ErbB3- and ErbB4-receptor tyrosine kinases. However, NRG-2 stimulates different ErbB-receptor tyrosine-phosphorylation profiles from NRG-1. Our results indicate that NRG-1 and NRG-2 mediate distinct biological processes by acting at different sites in tissues and eliciting different biochemical responses in cells.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Brain / metabolism
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Cell Adhesion
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Dimerization
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Epidermal Growth Factor / metabolism*
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ErbB Receptors / metabolism*
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Glycoproteins / metabolism*
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Humans
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Ligands
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Mice
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Mice, Inbred C57BL
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Molecular Sequence Data
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Myocardium / metabolism
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Nerve Growth Factors / metabolism*
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Neuregulins
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Phosphorylation
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Proto-Oncogene Proteins / metabolism*
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Receptor, ErbB-3
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Receptor, ErbB-4
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Sequence Homology, Amino Acid
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Tumor Cells, Cultured
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Tyrosine / metabolism
Substances
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Glycoproteins
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Ligands
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Nerve Growth Factors
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Neuregulins
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Proto-Oncogene Proteins
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Recombinant Proteins
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Tyrosine
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Epidermal Growth Factor
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ERBB4 protein, human
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ErbB Receptors
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Erbb4 protein, mouse
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Receptor, ErbB-3
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Receptor, ErbB-4