Research Article
AMP-activated Protein Kinase Subunit Interactions
β1:γ1 ASSOCIATION REQUIRES β1 Thr-263 AND Tyr-267

Tristan J. Iseli, Jonathan S. Oakhill, Michael F. Bailey, Sheena Wee, Mark Walter, Bryce J. van Denderen, Laura A. Castelli, Frosa Katsis, Lee A. Witters, David Stapleton, S. Lance Macaulay, Belinda J. Michell and Bruce E. Kemp

The Journal of Biological Chemistry, 2008, 283(8), 4799-4807. DOI: 10.1074/jbc.M708298200

Abstract

AMP-activated protein kinase (AMPK) plays multiple roles in the body`s overall metabolic balance and response to exercise, nutritional stress, hormonal stimulation, and the glucose-lowering drugs metformin and rosiglitazone. AMPK consists of a catalytic α subunit and two non-catalytic subunits, β and γ, each with multiple isoforms that form active 1:1:1 heterotrimers. Here we show that recombinant human AMPK α1β1γ1 expressed in insect cells is monomeric and displays specific activity and AMP responsiveness similar to rat liver AMPK. The previously determined crystal structure of the core of mammalian αβγ complex shows that β binds α and γ. Here we show that a β1(186–270)γ1 complex can form in the absence of detectable α subunit. Moreover, using alanine mutagenesis we show that β1 Thr-263 and Tyr-267 are required for βγ association but not αβ association.

ASCI-ID: 188-611

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