PUBLICATION
Duplicated zebrafish insulin-like growth factor binding protein-5 genes with split functional domains: evidence for evolutionarily conserved IGF binding, nuclear localization, and transactivation activity
- Authors
- Dai, W., Kamei, H., Zhao, Y., Ding, J., Du, Z., and Duan, C.
- ID
- ZDB-PUB-100119-23
- Date
- 2010
- Source
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology 24(6): 2020-2029 (Journal)
- Registered Authors
- Duan, Cunming
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Cell Nucleus/metabolism*
- Cloning, Molecular
- Cytoplasm/metabolism
- Evolution, Molecular
- Genes, Duplicate*
- In Situ Hybridization
- Insulin-Like Growth Factor Binding Protein 5/genetics*
- Insulin-Like Growth Factor Binding Protein 5/metabolism
- Insulin-Like Growth Factor I/metabolism*
- Molecular Sequence Data
- Nuclear Localization Signals/metabolism*
- Phylogeny
- Protein Isoforms
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Reverse Transcriptase Polymerase Chain Reaction
- Sequence Homology, Amino Acid
- Transcriptional Activation
- Zebrafish/genetics*
- Zebrafish/growth & development
- Zebrafish/metabolism
- PubMed
- 20081093 Full text @ FASEB J.
Citation
Dai, W., Kamei, H., Zhao, Y., Ding, J., Du, Z., and Duan, C. (2010) Duplicated zebrafish insulin-like growth factor binding protein-5 genes with split functional domains: evidence for evolutionarily conserved IGF binding, nuclear localization, and transactivation activity. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 24(6):2020-2029.
Abstract
Insulin-like growth factor binding protein (IGFBP)-5 is a secreted protein that binds to IGF and modulates IGF actions. IGFBP-5 is also found in the nucleus of mammalian cells and has transactivation activity. The structural basis of this transactivation activity and its role in mediating IGF-independent actions are not clear. Here we report that there are 2 igfbp-5 genes in zebrafish and other teleost fish. In zebrafish, igfbp-5a and -5b are expressed in spatially restricted, mostly nonoverlapping domains during early development. The IGF binding site is conserved in both zebrafish IGFBP-5s, and they are both secreted and capable of IGF binding. Both proteins contain a consensus bipartite nuclear localization signal and were found in the nucleus when introduced into cultured cells. Although zebrafish IGFBP-5b possesses transactivation activity, zebrafish IGFBP-5a lacks this activity. Mutational analysis demonstrated that 2 unique amino acids in positions 22 and 56 of IGFBP-5a are responsible for its lack of transactivation activity. These findings suggest that the duplicated zebrafish IGFBP-5s have evolved divergent regulatory mechanisms and distinct biological properties by partitioning of ancestral structural domains and provide new evidence for a conserved role of the IGF binding, nuclear localization, and transactivation domain of this multifunctional IGFBP.-Dai, W., Kamei, H., Zhao, Y., Ding, J., Du, Z., Duan, C. Duplicated zebrafish insulin-like growth factor binding protein-5 genes with split functional domains: evidence for evolutionarily conserved IGF binding, nuclear localization, and transactivation activity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping