ZFIN ID: ZDB-PUB-000111-5
Insulin-like growth factor binding protein 2 is a growth inhibitory protein conserved in zebrafish
Duan, C.M., Ding, J., Li, Q., Tsai, W., and Pozios, K.
Date: 1999
Source: Proceedings of the National Academy of Sciences of the United States of America   96(26): 15274-15279 (Journal)
Registered Authors: Duan, Cunming
Keywords: none
MeSH Terms:
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Conserved Sequence*
  • Culture Media, Conditioned/pharmacology
  • Gene Expression
  • Gene Expression Regulation
  • Gene Library
  • Growth Hormone/pharmacology
  • Growth Inhibitors/genetics*
  • Insulin-Like Growth Factor Binding Protein 2/genetics*
  • Insulin-Like Growth Factor I/antagonists & inhibitors
  • Molecular Sequence Data
  • Nutritional Physiological Phenomena
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Tissue Distribution
  • Zebrafish/genetics*
PubMed: 10611375 Full text @ Proc. Natl. Acad. Sci. USA
Fish serum contains several specific binding proteins for insulin-like growth factors (IGFBPs). The structure and physiological function of these fish IGFBPs are unknown. Here we report the complete primary sequence of a zebrafish IGFBP deduced from cDNA clones isolated by library screening and rapid amplification of cDNA ends. The full-length 1,757-bp cDNA encodes a protein of 276 aa, which contains a putative 22-residue signal peptide and a 254-residue mature protein. The mature zebrafish IGFBP has a predicted molecular size of 28,440 Da and shows high sequence identity with human IGFBP-2 (52%). The sequence identities with other human IGFBPs are <37%. Chinese hamster ovary cells stably transfected with the zebrafish IGFBP-2 cDNA secreted a 31-kDa protein, which bound to IGF-I and IGF-II with high affinity, but did not bind to Des(1-3)IGF-I or insulin. Northern blot analyses revealed that the zebrafish IGFBP-2 transcript is a 1.8-kb band expressed in many embryonic and adult tissues. In adult zebrafish, IGFBP-2 mRNA levels were greatly reduced by growth hormone treatment but increased by prolonged fasting. When overexpressed or added to cultured zebrafish and mammalian cells, the zebrafish IGFBP-2 significantly inhibited IGF-I-stimulated cell proliferation and DNA synthesis. These results indicate that zebrafish IGFBP-2 is a negative growth regulator acting downstream in the growth hormone-IGF-I axis.