Abstract

The PC12 cell line is a cloned line derived from a rat pheochromocytoma that has proved to be a useful model system to study the regulation of neural development. A number of neural properties (neurotransmitter synthesis, neurite extension, enzyme induction, cell division and neurosecretion) are regulated by adenosine in PC12 cells. The major mediator of adenosine in these cells is cAMP. The central objective of this grant is to establish the roles of the cAMP-dependent kinases in regulation of neural properties in these cells. To do this, we will isolate mutants that are: defective in the regulation of cAMP production, defective in one or more of the cAMP-dependent protein kinases, or defective in a regulatory step subsequent to the activation of the cAMP-dependent protein kinases. We will establish the biochemical nature of the defect in these mutants and determine the effect of each mutation on the regulation of the differentiated properties of the cells by adenosine or cAMP analogues.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA040929-02
Application #
3181241
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1985-09-01
Project End
1988-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Boniece, I R; Wagner, J A (1995) NGF protects PC12 cells against ischemia by a mechanism that requires the N-kinase. J Neurosci Res 40:1-9
Boniece, I R; Wagner, J A (1993) Growth factors protect PC12 cells against ischemia by a mechanism that is independent of PKA, PKC, and protein synthesis. J Neurosci 13:4220-8
Scheibe, R J; Wagner, J A (1992) Retinoic acid regulates both expression of the nerve growth factor receptor and sensitivity to nerve growth factor. J Biol Chem 267:17611-6
Hawley, R J; Scheibe, R J; Wagner, J A (1992) NGF induces the expression of the VGF gene through a cAMP response element. J Neurosci 12:2573-81
Glowacka, D; Ginty, D D; Wagner, J A (1992) Synergistic effects of nerve growth factor and phorbol 12-myristate 13-acetate on rapid motility and process formation in PC12 cells: the role of laminin. J Neurosci Res 31:263-72
Ginty, D D; Fanger, G R; Wagner, J A et al. (1992) The activity of cAMP-dependent protein kinase is required at a posttranslational level for induction of voltage-dependent sodium channels by peptide growth factors in PC12 cells. J Cell Biol 116:1465-73
Damon, D H; Halegoua, S; D'Amore, P et al. (1992) Rapid fibroblast growth factor-induced increases in protein phosphorylation and ornithine decarboxylase activity: regulation by heparin and comparison to nerve growth factor-induced increases. Exp Cell Res 201:154-9
Ginty, D D; Glowacka, D; DeFranco, C et al. (1991) Nerve growth factor-induced neuronal differentiation after dominant repression of both type I and type II cAMP-dependent protein kinase activities. J Biol Chem 266:15325-33
Ginty, D D; Glowacka, D; Bader, D S et al. (1991) Induction of immediate early genes by Ca2+ influx requires cAMP-dependent protein kinase in PC12 cells. J Biol Chem 266:17454-8
Roth, J A; Marcucci, K; Lin, W H et al. (1991) Increase in beta-1,4-galactosyltransferase activity during PC12 cell differentiation induced by forskolin and 2-chloroadenosine. J Neurochem 57:708-13

Showing the most recent 10 out of 14 publications