Neuregulin-3 (NRG3): A novel neural tissue-enriched protein that binds and activates ErbB4

被引:305
作者
Zhang, DX
Sliwkowski, MX
Mark, M
Frantz, G
Akita, R
Sun, Y
Hillan, K
Crowley, C
Brush, J
Godowski, PJ
机构
[1] GENENTECH INC, DEPT MOL BIOL, San Francisco, CA 94080 USA
[2] GENENTECH INC, DEPT PROT CHEM, San Francisco, CA 94080 USA
[3] GENENTECH INC, DEPT PATHOL, San Francisco, CA 94080 USA
关键词
D O I
10.1073/pnas.94.18.9562
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:9562 / 9567
页数:6
相关论文
共 44 条
[1]   THE STRUCTURAL BASIS FOR THE SPECIFICITY OF EPIDERMAL GROWTH-FACTOR AND HEREGULIN BINDING [J].
BARBACCI, EG ;
GUARINO, BC ;
STROH, JG ;
SINGLETON, DH ;
ROSNACK, KJ ;
MOYER, JD ;
ANDREWS, GC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (16) :9585-9589
[2]   Epidermal growth factor-related peptides activate distinct subsets of ErbB receptors and differ in their biological activities [J].
Beerli, RR ;
Hynes, NE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (11) :6071-6076
[3]  
BerminghamMcDonogh O, 1996, DEVELOPMENT, V122, P1427
[4]   INTRACELLULAR PROTEIN TOPOGENESIS [J].
BLOBEL, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1980, 77 (03) :1496-1500
[5]  
CARRAWAY KL, 1994, J BIOL CHEM, V269, P14303
[6]   A NEU ACQUAINTANCE FOR ERBB3 AND ERBB4 - A ROLE FOR RECEPTOR HETERODIMERIZATION IN GROWTH SIGNALING [J].
CARRAWAY, KL ;
CANTLEY, LC .
CELL, 1994, 78 (01) :5-8
[7]   Neuregulin-2, a new ligand of ErbB3/ErbB4-receptor tyrosine kinases [J].
Carraway, KL ;
Weber, JL ;
Unger, MJ ;
Ledesma, J ;
Yu, N ;
Gassmann, M ;
Lai, C .
NATURE, 1997, 387 (6632) :512-516
[8]   HUMANIZATION OF AN ANTI-P185HER2 ANTIBODY FOR HUMAN CANCER-THERAPY [J].
CARTER, P ;
PRESTA, L ;
GORMAN, CM ;
RIDGWAY, JBB ;
HENNER, D ;
WONG, WLT ;
ROWLAND, AM ;
KOTTS, C ;
CARVER, ME ;
SHEPARD, HM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (10) :4285-4289
[9]   Ligands for ErbB-family receptors encoded by a neuregulin-like gene [J].
Chang, H ;
Riese, DJ ;
Gilbert, W ;
Stern, DF ;
McMahan, UJ .
NATURE, 1997, 387 (6632) :509-512
[10]   HUMAN TRANSFORMING GROWTH FACTOR-ALPHA - PRECURSOR STRUCTURE AND EXPRESSION IN ESCHERICHIA-COLI [J].
DERYNCK, R ;
ROBERTS, AB ;
WINKLER, ME ;
CHEN, EY ;
GOEDDEL, DV .
CELL, 1984, 38 (01) :287-297