The immunoglobulin-like domain is involved in interaction of Neuregulin1 with ErbB.
Neuregulin1 (NRG1) is a growth factor that signals through the interaction of the epidermal growth factor (EGF)-like domain with ErbB receptors. An immunoglobulin (Ig)-like domain is contained together with EGF-like domain in the ectodomain of some isoforms generated by alternative splicing, but its role in NRG1 signaling remained unclear. In the present study, we identified a novel isoform of NRG1 containing an Ig-like domain conserved among species from adult Xenopus laevis, which is predominantly expressed in the testis and brain. We generated recombinant proteins for the whole ectodomain and EGF-like domain alone of the isoform to compare their effects on cell proliferation, and phosphorylation of and their association with ErbB receptor, demonstrating that the ectodomain had approximately 10(3)-fold higher abilities than the EGF-like domain. Therefore, the Ig-like domain is probably essential for efficient interaction of an EGF-like domain with ErbB receptors.
Eto
Ko
K
Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Kumamoto 860-8555, Japan. etoko@gpo.kumamoto-u.ac.jp
Eda
Kazufumi
K
Kanemoto
Shintaro
S
Abe
Shin-Ichi
S
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003001:Cloning, Molecular; D066246:ErbB Receptors / Q000378:metabolism*; D007136:Immunoglobulins / Q000737:chemistry*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D020890:Neuregulin-1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D066247:Receptor, ErbB-4; D016415:Sequence Alignment; D013737:Testis / Q000378:metabolism; D014018:Tissue Distribution; D029867:Xenopus Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
D007136:Immunoglobulins; D020890:Neuregulin-1; D020033:Protein Isoforms; D012333:RNA, Messenger; D029867:Xenopus Proteins; D066246:ErbB Receptors; C587690:Erbb4 protein, mouse; D066247:Receptor, ErbB-4