Manipulation of protein kinases reveals different mechanisms for upregulation of heat shock proteins in motor neurons and non-neuronal cells.

TitleManipulation of protein kinases reveals different mechanisms for upregulation of heat shock proteins in motor neurons and non-neuronal cells.
Publication TypeJournal Article
Year of Publication2007
AuthorsTaylor DM, De Koninck P, Minotti S, Durham HD
JournalMol Cell Neurosci
Volume34
Issue1
Pagination20-33
Date Published2007 Jan
ISSN1044-7431
KeywordsAnimals, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Calcium-Calmodulin-Dependent Protein Kinase Type 4, Calcium-Calmodulin-Dependent Protein Kinases, Cell Nucleus, Cells, Cultured, DNA-Binding Proteins, Enzyme Activation, Fibroblasts, Gene Expression Regulation, Enzymologic, Genes, Reporter, Glycogen Synthase Kinase 3, Green Fluorescent Proteins, Heat-Shock Proteins, Heat-Shock Response, HSP70 Heat-Shock Proteins, Mice, Motor Neurons, Promoter Regions, Genetic, Protein Kinase C, Protein Kinases, Stress, Physiological, Transcription Factors, Up-Regulation
Abstract

Motor neurons have a high threshold for induction of heat shock proteins (Hsps) in response to stress, a property associated with impaired ability to activate heat shock transcription factor 1 (Hsf1). Hyperphosphorylation of Hsf1 has been established as a requirement for transactivation of heat shock genes. This study demonstrated that the impaired heat shock response in motor neurons is not due to altered phosphorylation of Hsf1 by kinases previously shown to affect activation of Hsf1 in other cells (PKC, GSK3beta, ERK1, CaMKIIalpha). However, a constitutively active form of CaMKIV induced robust expression of Hsp70, as well as transcription of a GFP reporter gene driven by the human inducible Hsp70 promoter in unstressed motor neurons, but not in mouse embryonic fibroblasts. The results point to novel mechanisms of activation of heat shock genes in motor neurons that have relevance to exploitation of endogenous stress responses therapeutically.

DOI10.1016/j.mcn.2006.09.007
Alternate JournalMol. Cell. Neurosci.
PubMed ID17113785

Funding

Our research endeavors are made possible by the following agencies:

Canadian Institutes of Health Research - Instituts de recherche en santé du Canada Fonds de recherche du Québec – Nature et technologies (FRQNT)Fonds de la recherche en santé du Québec NARSAD Natural Sciences and Engineering Research Council of Canada (NSERC) - Conseil de recherche en sciences naturelles et en génie du Canada (CRSNG)innovation.caHuman Frontier Science Program