Mnk kinase homologous proteins involved in the regulation of energy homeostasis and organelle metabolism

A method of screening for an agent which increases or decreases the kinase activity of an Mnk protein selected from Mnk2a, Mnk2b, and Mnkl, or a protein fragment thereof, wherein said protein fragment has the kinase activity of the Mnk protein, the method comprising the steps of:

• (a) providing a mixture not having a candidate agent, said mixture comprising:
• a Mnk protein selected from Mnk2a, Mnk2b, and Mnk1, or a fragment thereof, wherein said Mnk protein, or fragment thereof has a kinase activity;
• a kinase substrate capable of being phosphorylated by said Mnk protein, or fragment thereof;
• and a suitable reaction buffer comprising a donor molecule having a radioisotopically labeled phosphate group thereon;
• (b) incubating said mixture for a period of time;
• (c) determining the level of phosphorylation of the kinase substrate at a first time point and at least one subsequent time point;
• (d) comparing the level of phosphorylation of the kinase substrate at the first time point and at the subsequent time point, thereby determining the level of the kinase activity of said Mnk protein, or fragment thereof in the absence of a candidate agent;
• (e) repeating steps (a)-(d) in the presence of a candidate agent, thereby determining the level of the kinase activity of said Mnk protein, or fragment thereof in the presence of the candidate agent, and wherein the candidate agent is selected from the group consisting of:
• an antibody, an aptamer, an antisense molecule, a ribozyme, an iRNA, and a small organic compound having a molecular weight of more than 50 Da and less than about 2500 Da;
• and
• (f) comparing the level of the kinase activity obtained in the absence of the candidate agent with the level in the presence of the candidate agent, whereby an increase in the level of kinase activity in the presence of the candidate agent compared to the level in the absence thereof indicates that the candidate agent is an activator of said kinase activity, and a decrease in the level of kinase activity in the presence of the candidate agent compared to the level in the absence thereof indicates that the candidate agent is an inhibitor of said kinase activity, thereby identifying the candidate agent as a modifier of the kinase activity of an Mnk protein, or a protein fragment thereof, associated with a disease or disorder of body-weight regulation or thermogenesis, said disease or disorder selected from obesity, eating disorder, cachexia, diabetes mellitus, hypertension, coronary heart disease, hypercholesterolemia, and dyslipidemia.