TI - Regulation of phosphoglucomutase 1 phosphorylation and activity by a signaling kinase . AB - We have identified a novel mechanism of cross-talk between cell signaling and metabolic pathways , whereby the signaling kinase p21-activated kinase 1 ( Pak1 ) binds to , phosphorylates and enhances the enzymatic activity of phosphoglucomutase 1 ( PGM ) , an important regulatory enzyme in cellular glucose utilization and energy homeostasis . Pak1 and PGM were colocalized in model cell systems and showed functional interactions in a physiological setting . Strong direct interaction of PGM with Pak1 but not Pak2 , Pak3 , or Pak4 was observed . PGM binding was within 75-149 amino acids ( aa ) of Pak1 , while Pak1 binding to PGM was in the N-terminal 96 aa . Pak1 -mediated phosphorylation of PGM selectively on threonine 466 significantly increased PGM enzymatic activity and could be blocked by transfection with a dominant-negative Pak1 expression vector and by Pak1-specific small inhibitory RNA . Stable transfection of PGM into PGM-deficient K562 leukemia cells further demonstrated the role of Pak1 in regulating PGM activity . The results presented here provide new evidence that the cell signaling kinase Pak1 is a novel regulator of glucose metabolism through its phosphorylation and regulation of PGM activity . These findings suggest a new mechanism whereby growth factor signaling may coordinately integrate metabolic regulation with established signaling functions of cell cycle regulation and cell growth .