PUBLICATION
Insulin-like growth factor binding protein 2 is a growth inhibitory protein conserved in zebrafish
- Authors
- Duan, C.M., Ding, J., Li, Q., Tsai, W., and Pozios, K.
- ID
- ZDB-PUB-000111-5
- 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
Citation
Duan, C.M., Ding, J., Li, Q., Tsai, W., and Pozios, K. (1999) Insulin-like growth factor binding protein 2 is a growth inhibitory protein conserved in zebrafish. Proceedings of the National Academy of Sciences of the United States of America. 96(26):15274-15279.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping