Neuregulin-4: a novel growth factor that acts through the ErbB-4 receptor tyrosine kinase

被引:264
作者
Harari, D
Tzahar, E
Romano, J
Shelly, M
Pierce, JH
Andrews, GC
Yarden, Y [1 ]
机构
[1] Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel
[2] NCI, Bethesda, MD 20892 USA
[3] Pfizer Inc, Cent Res, Groton, CT 06340 USA
基金
以色列科学基金会;
关键词
growth factor; oncogene; pancreas; signal transduction; tyrosine kinase;
D O I
10.1038/sj.onc.1202631
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The ErbB/HER family of receptor tyrosine kinases consists of four receptors that bind a large number of growth factor ligands sharing an epidermal growth factor- (EGF)-like motif, Whereas ErbB-1 binds seven different ligands whose prototype is EGF, the three families of neuregulins (NRGs) activate ErbB-3 and/or ErbB-4. Here we characterize a fourth neuregulin, NRG-4, that acts through ErbB-4. The predicted pro-NRG-4 is a transmembrane protein carrying a unique EGF-like motif and a short cytoplasmic domain. A synthetic peptide encompassing the full-length EGF-like domain can induce growth of interleukin-dependent cells ectopically expressing ErbB-4, but not cells expressing the other three ErbB proteins or their combinations. Consistent with specificity to ErbB-4, NRG-4 can displace an ErbB-4-bound NRG-1 and can activate signaling downstream of this receptor, Expression of NRG-4 mRNA was detected in the adult pancreas and weakly in muscle; other tissues displayed no detectable NRG-4 mRNA. The primary structure and the pattern of expression of NRG-4, together with the strict specificity of this growth factor to ErbB-4, suggest a physiological role distinct from that of the known ErbB ligands.
引用
收藏
页码:2681 / 2689
页数:9
相关论文
共 60 条
[1]   Epidermal growth factor and betacellulin mediate signal transduction through co-expressed ErbB2 and ErbB3 receptors [J].
Alimandi, M ;
Wang, LM ;
Bottaro, D ;
Lee, CC ;
Kuo, A ;
Frankel, M ;
Fedi, P ;
Tang, C ;
Lippman, M ;
Pierce, JH .
EMBO JOURNAL, 1997, 16 (18) :5608-5617
[2]   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
[3]  
Ben-Baruch Noa, 1998, P145
[4]   Neuregulins and their receptors: A versatile signaling module in organogenesis and oncogenesis [J].
Burden, S ;
Yarden, Y .
NEURON, 1997, 18 (06) :847-855
[5]   Characterization of a neuregulin-related gene, Don-1, that is highly expressed in restricted regions of the cerebellum and hippocampus [J].
Busfield, SJ ;
Michnick, DA ;
Chickering, TW ;
Revett, TL ;
Ma, JY ;
Woolf, EA ;
Comrack, CA ;
Dussault, BJ ;
Woolf, J ;
Goodearl, ADJ ;
Gearing, DP .
MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (07) :4007-4014
[6]   EPIDERMAL GROWTH-FACTOR [J].
CARPENTER, G ;
COHEN, S .
ANNUAL REVIEW OF BIOCHEMISTRY, 1979, 48 :193-216
[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]   HEREGULIN ACTIVATION OF EXTRACELLULAR ACIDIFICATION IN MAMMARY-CARCINOMA CELLS IS ASSOCIATED WITH EXPRESSION OF HER2 AND HER3 [J].
CHAN, SDH ;
ANTONIUCCI, DM ;
FOK, KS ;
ALAJOKI, ML ;
HARKINS, RN ;
THOMPSON, SA ;
WADA, HG .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (38) :22608-22613
[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]   An immunological approach reveals biological differences between the two NDF/heregulin receptors, ErbB-3 and ErbB4 [J].
Chen, XM ;
Levkowitz, G ;
Tzahar, E ;
Karunagaran, D ;
Lavi, S ;
BenBaruch, N ;
Leitner, O ;
Ratzkin, BJ ;
Bacus, SS ;
Yarden, Y .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (13) :7620-7629