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Regulation of phosphoglucomutase 1 phosphorylation and activity by a signaling kinase

Oncogene volume 23, pages 8118–8127 (2004)Cite this article

Abstract

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.

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Acknowledgements

We thank Dr Richard B Marchase for providing a PGM antibody. This work was supported by the NIH grant CA 90970 and CA80066 (RK).

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  1. Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, 77030, TX, USA

    Anupama Gururaj, Christopher J Barnes, Ratna K Vadlamudi & Rakesh Kumar

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  1. Anupama Gururaj
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  3. Ratna K Vadlamudi
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Correspondence to Rakesh Kumar.

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Gururaj, A., Barnes, C., Vadlamudi, R. et al. Regulation of phosphoglucomutase 1 phosphorylation and activity by a signaling kinase. Oncogene 23, 8118–8127 (2004). https://doi.org/10.1038/sj.onc.1207969

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