Regulation of phosphoglucomutase 1 phosphorylation and activity by a signaling kinase

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

Research output: Contribution to journalArticle

62 Citations (Scopus)

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 96aa. 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 K-562 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.

Original languageEnglish (US)
Pages (from-to)8118-8127
Number of pages10
JournalOncogene
Volume23
Issue number49
DOIs
StatePublished - Oct 21 2004
Externally publishedYes

Fingerprint

Phosphoglucomutase
p21-Activated Kinases
Phosphotransferases
Phosphorylation
Transfection
Glucose
Threonine
Metabolic Networks and Pathways
Intercellular Signaling Peptides and Proteins
Cell Cycle
Leukemia
Homeostasis

Keywords

  • Cancer metabolism
  • Glycolysis
  • PGM
  • Signaling

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Regulation of phosphoglucomutase 1 phosphorylation and activity by a signaling kinase. / Gururaj, Anupama; Barnes, Christopher J.; Vadlamudi, Ratna K; Kumar, Rakesh.

In: Oncogene, Vol. 23, No. 49, 21.10.2004, p. 8118-8127.

Research output: Contribution to journalArticle

Gururaj, Anupama ; Barnes, Christopher J. ; Vadlamudi, Ratna K ; Kumar, Rakesh. / Regulation of phosphoglucomutase 1 phosphorylation and activity by a signaling kinase. In: Oncogene. 2004 ; Vol. 23, No. 49. pp. 8118-8127.
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