Characterization of the CaMKKβ-AMPK signaling complex.

Published

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

  • 21807092

Electronic International Standard Serial Number (EISSN)

  • 1873-3913

Digital Object Identifier (DOI)

  • 10.1016/j.cellsig.2011.07.014

Language

  • eng

Conference Location

  • England