Abstract

Three specific aims are proposed that will address these important unresolved issues. 1) The mechanism by which NGF induced phosphorylation of Elk-1 and CREB triggers c-fos transcription will be investigated. 2) The role that phosphorylation and protein: protein interactions play in regulating the CREB kinase will be characterized. 3) The importance of the ERKS and Elk-1, and CREB kinase and CREB as mediators of neuronal differentiation and survival will be explored. Given the critical role that NGF plays in nervous system development and the important of IEGs in the control of cell growth and differentiation, the proposed experiments have the potential to give new insight into how the deregulation of these processes can lead to neural degeneration or oncogenesis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA043855-14
Application #
6163903
Study Section
Special Emphasis Panel (ZRG1-NEUC (02))
Program Officer
Freeman, Colette S
Project Start
1986-12-01
Project End
2002-02-28
Budget Start
2000-03-01
Budget End
2001-02-28
Support Year
14
Fiscal Year
2000
Total Cost
$386,242
Indirect Cost

  Institution

Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Takasu, Mari A; Dalva, Matthew B; Zigmond, Richard E et al. (2002) Modulation of NMDA receptor-dependent calcium influx and gene expression through EphB receptors. Science 295:491-5
Zhu, J W; Field, S J; Gore, L et al. (2001) E2F1 and E2F2 determine thresholds for antigen-induced T-cell proliferation and suppress tumorigenesis. Mol Cell Biol 21:8547-64
Murga, M; Fernandez-Capetillo, O; Field, S J et al. (2001) Mutation of E2F2 in mice causes enhanced T lymphocyte proliferation, leading to the development of autoimmunity. Immunity 15:959-70
Brunet, A; Park, J; Tran, H et al. (2001) Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a). Mol Cell Biol 21:952-65
Shamah, S M; Lin, M Z; Goldberg, J L et al. (2001) EphA receptors regulate growth cone dynamics through the novel guanine nucleotide exchange factor ephexin. Cell 105:233-44
Sun, Y; Nadal-Vicens, M; Misono, S et al. (2001) Neurogenin promotes neurogenesis and inhibits glial differentiation by independent mechanisms. Cell 104:365-76
Brunet, A; Datta, S R; Greenberg, M E (2001) Transcription-dependent and -independent control of neuronal survival by the PI3K-Akt signaling pathway. Curr Opin Neurobiol 11:297-305
Dalva, M B; Takasu, M A; Lin, M Z et al. (2000) EphB receptors interact with NMDA receptors and regulate excitatory synapse formation. Cell 103:945-56
Shaywitz, A J; Dove, S L; Kornhauser, J M et al. (2000) Magnitude of the CREB-dependent transcriptional response is determined by the strength of the interaction between the kinase-inducible domain of CREB and the KIX domain of CREB-binding protein. Mol Cell Biol 20:9409-22
Brunet, A; Bonni, A; Zigmond, M J et al. (1999) Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96:857-68

Showing the most recent 10 out of 37 publications