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Letters to Nature
Nature 387, 512 - 516 (29 May 1997); doi:10.1038/387512a0

Neuregulin-2, a new ligand of ErbB3/ErbB4-receptor tyrosine kinases

Kermit L. Carraway III*, Janet L. Weber, Michelle J. Unger*, Jessica Ledesma, Naichen Yu, Martin Gassmann§ & Cary Lai

*Department of Cell Biology) Harvard Medical School, and Division of Signal Transduction, Beth Israel Hospital, Boston, Massachusetts 02215, USA
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA
Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, California 92037, USA
§ Present address: Division of Neurobiology, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.

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.

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