Characterization of the CaMKKβ-AMPK signaling complex.
Journal Article (Journal Article)
The AMP-activated protein kinase (AMPK) is a critical regulator of energy homeostasis, and is a potential target for treatment of metabolic diseases as well as cancer. AMPK can be phosphorylated and activated by the tumor suppressor LKB1 or the Ca(2+)/CaM-dependent protein kinase kinase β (CaMKKβ). We previously identified a physical complex between CaMKKβ and AMPK (Anderson, K. A., Ribar, T. J., Lin, F., Noeldner, P. K., Green, M. F., Muehlbauer, M. J., Witters, L. A., Kemp, B. E., and Means, A. R. (2008) Cell Metabolism 7, 377-388). Here we expand our analysis of the CaMKKβ-AMPK signaling complex and show that whereas CaMKKβ can form a complex with and activate AMPK, CaMKKα cannot. In addition, we show that CaMKKβ and AMPK associate through their kinase domains, and CaMKKβ must be in an active conformation in order to bind AMPK but not to associate with an alternative substrate, Ca(2+)/Calmodulin-dependent protein kinase IV (CaMKIV). Our results demonstrate that CaMKKβ and AMPK form a unique signaling complex. This raises the possibility that the CaMKKβ-AMPK complex can be specifically targeted by small molecule drugs to treat disease.
Full Text
Duke Authors
Cited Authors
- Green, MF; Anderson, KA; Means, AR
Published Date
- December 2011
Published In
Volume / Issue
- 23 / 12
Start / End Page
- 2005 - 2012
PubMed ID
- 21807092
Pubmed Central ID
- PMC3184326
Electronic International Standard Serial Number (EISSN)
- 1873-3913
Digital Object Identifier (DOI)
- 10.1016/j.cellsig.2011.07.014
Language
- eng
Conference Location
- England