M2-PK can be phosphorylated in serine.

With the yeast two hybrid technique M2-PK was identified as a target of the A-Raf kinase. The interaction between M2-PK and A-Raf takes place via the C-terminal kinase domain of A-Raf.

B-Raf and c-Raf did not interact with M2-PK within the yeast two hybrid test.

The effect of A-Raf on the tetramer : dimer ratio of M2-PK seems to depend on the glutamine and serine metabolism of the individual cell line.

Serine is synthesized from the glycolytic intermediate glycerate 3-P and glutamate, a degradation product of glutamine. 
During serine degradation (serinolysis) the amino group of serine is transferred on pyruvate with the production of alanine. The carbons of serine are channeled into glycolysis and converted to lactate.

In primary mouse fibroblasts which were characterized by glutamine production and serine consumption, expression of A-Raf wildtype induced a dimerization and inactivation of M2-PK which was accompanied by a reduction of the flux from glucose to lactate.

Metabolic scheme: A-Raf wildtype primary mouse fibroblasts

In NIH 3T3 cells which were characterized by glutamine consumption, as well as serine production transformation with constitutively active A-Raf (fusion protein between the kinase domain of A-Raf and the retroviral gag-protein) induced a tetramerization and activation of M2-PK which resulted in an increased flux of glucose to lactate.

Metabolic scheme: gag-A-Raf transformed NIH 3T3 cells

High serine levels induce an activation of M2-PK. Therefore, the tetramerization and activation of M2-PK in gag-A-Raf transformed NIH 3T3 cells may be a secondary metabolic effect induced by high serine levels.

Co-transfection of NIH 3T3 cells with gag-A-Raf and a kinase dead mutant of M2-PK reduced colony formation whereas co-transfection with wildtype M2-PK led to a doubling of colony formation which points to a cooperative effect of A-Raf and M2-PK in cell transformation.

References

M2-PK: a target of different oncoproteins