AMP-activated protein kinase subunit interactions - beta 1 :gamma 1 association requires beta 1 Thr-263 and Tyr-267

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

来源：Journal of Biological Chemistry, 2008, 283(8): 4799-4807.

DOI：10.1074/jbc.M708298200

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 alpha subunit and two non-catalytic subunits, beta and gamma, each with multiple isoforms that form active 1: 1: 1 heterotrimers. Here we show that recombinant human AMPK alpha 1 beta 1 gamma 1 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 alpha beta gamma complex shows that beta binds alpha and gamma. Here we show that a beta 1(186-270)gamma 1 complex can form in the absence of detectable alpha subunit. Moreover, using alanine mutagenesis we show that beta 1 Thr-263 and Tyr-267 are required for beta gamma association but not alpha beta association.

• 出版日期2008-2-22
• 单位CSIRO