PUBLICATION
Roles for FRAP in phosphatase regulation, translation initiation, and vertebrate development
- Authors
- Peterson, R.T.
- ID
- ZDB-PUB-021016-50
- Date
- 2000
- Source
- Ph.D. Thesis : (Thesis)
- Registered Authors
- Peterson, Randall
- Keywords
- none
- MeSH Terms
- none
- PubMed
- none
Citation
Peterson, R.T. (2000) Roles for FRAP in phosphatase regulation, translation initiation, and vertebrate development. Ph.D. Thesis. .
Abstract
The binding of the FKBP12-rapamycin complex to the FKBP12-rapamycin-associated protein (FRAP) affects several biological processes including translation initiation. The studies described herein seek to understand the mechanisms by which FRAP influences translation. Identification of a FRAP autophosphorylation site provided an assay for the study of factors that may regulate FRAP autokinase activity. FRAP autokinase activity is not inhibited by rapamycin treatment nor serum withdrawal, two conditions proposed to regulate FRAP kinase activity. Instead, the association of the FKBP12-rapamycin complex with FRAP promotes the activation of the phosphatase PP2A, which binds to rapamycin-sensitive (but not rapamycin insensitive) forms of the translational regulator, p70 s6k. The ability of FRAP to regulate PP2A may depend on direct association of PP2A with FRAP and/or ?4. Multiple roles for FRAP in vertebrate development (including roles in chondrogenesis, nutrient usage, and an unidentified essential role) are also explored by modulating FRAP function in the developing zebrafish.
Errata / Notes
Ph.D. Thesis, Harvard University
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping