Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-6-2
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2020-9
pubmed:meshHeading
pubmed-meshheading:20081093-Amino Acid Sequence, pubmed-meshheading:20081093-Animals, pubmed-meshheading:20081093-Cell Nucleus, pubmed-meshheading:20081093-Cloning, Molecular, pubmed-meshheading:20081093-Cytoplasm, pubmed-meshheading:20081093-Evolution, Molecular, pubmed-meshheading:20081093-Genes, Duplicate, pubmed-meshheading:20081093-In Situ Hybridization, pubmed-meshheading:20081093-Insulin-Like Growth Factor Binding Protein 5, pubmed-meshheading:20081093-Insulin-Like Growth Factor I, pubmed-meshheading:20081093-Molecular Sequence Data, pubmed-meshheading:20081093-Nuclear Localization Signals, pubmed-meshheading:20081093-Phylogeny, pubmed-meshheading:20081093-Protein Isoforms, pubmed-meshheading:20081093-RNA, Messenger, pubmed-meshheading:20081093-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:20081093-Sequence Homology, Amino Acid, pubmed-meshheading:20081093-Transcriptional Activation, pubmed-meshheading:20081093-Zebrafish
pubmed:year
2010
pubmed:articleTitle
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.
pubmed:affiliation
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural