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Calcium/calmodulin-dependent protein kinase types II and IV differentially regulate CREB-dependent gene expression
R P Matthews1, C R Guthrie, L M Wailes
1Department of Pharmacology, University of Washington, Seattle 98195.
Molecular and Cellular Biology
|September 1, 1994
Summary
Calcium-dependent protein kinase type IV (CaMKIV) activates gene expression by entering the nucleus. This CaMKIV pathway is independent of cAMP-dependent protein kinase (PKA) and mediates calcium-induced gene induction.
Area of Science:
- Molecular Biology
- Cell Biology
- Neuroscience
Background:
- CREB (cyclic AMP response element-binding protein) activation by PKA is a known pathway for gene induction.
- Elevated intracellular Ca2+ can trigger CREB phosphorylation and promoter activation in certain cell types.
- Some cells lack Ca2+-mediated activation of CRE-containing promoters.
Purpose of the Study:
- To investigate the role of CaMKIV in mediating Ca2+-dependent gene induction.
- To determine if CaMKIV can confer Ca2+ responsiveness to cells lacking it.
- To compare the activity of CaMKIV and CaMKII in regulating CRE-containing promoters.
Main Methods:
- Transfection of cultured cells with expression vectors for CaMKIV or CaMKII.
- Utilizing a reporter gene assay to measure promoter activation.
- Examining the subcellular localization of CaMKIV and CaMKII.
Main Results:
- CaMKIV expression conferred Ca2+-mediated activation of a CRE-containing promoter.
- CaMKIV-mediated induction was dependent on CREB/ATF but independent of PKA.
- CaMKII did not mediate transactivation, and only CaMKIV localized to the nucleus.
Conclusions:
- CaMKIV acts as a mediator of Ca2+-dependent gene induction.
- CaMKIV's nuclear localization is crucial for its function in gene regulation.
- CaMKIV may play a significant role in neuronal, reproductive, and lymphoid tissues.