Cell proliferation depends on the direct binding between PKM2 and AKAP-Lbc

The M2 form of the glycolytic enzyme pyruvate kinase (PKM2) has generated much interest recently due to its important role in tumor metabolism. A yeast two-hybrid screen carried out by the Alliance for Cell Signaling suggests that PKM2 interacts with A-Kinase Anchoring Protein (AKAP)-Lbc. AKAP-Lbc (also known as AKAP13) is a scaffold protein that integrates signaling through multiple enzymes including protein kinases A and D and the small G protein Rho. AKAP-Lbc was originally identified in leukemic blast cells, and multiple reports implicate AKAP-Lbc in breast, prostate and thyroid cancers, however the role of AKAP-Lbc in cancer biology is not understood. Co-immunoprecipitation, pulldown and Bimolecular Fluorescence Complementation (BiFC) data indicate that PKM2 interacts with AKAP-Lbc. Mapping experiments indicate that PKM2 directly interacts with amino acid residues 1923-2817 of AKAP-Lbc. By disrupting the interaction between the two proteins with the expression of the AKAP-Lbc fragments, our data suggest that the binding between PKM2 and PKA plays a critical role in cell proliferation. The work indicates that the binding between AKAP-Lbc and PKM2 may be an important target to treat some cancers by reducing the cell proliferation.