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Regulation of phosphoglucomutase 1 phosphorylation and activity by a signaling kinase
- Source :
- Oncogene. 23:8118-8127
- Publication Year :
- 2004
- Publisher :
- Springer Science and Business Media LLC, 2004.
-
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.
- Subjects :
- Cancer Research
Cell signaling
Protein Conformation
Molecular Sequence Data
Protein Serine-Threonine Kinases
Biology
PAK1
Cell Line, Tumor
Genetics
Humans
Amino Acid Sequence
Phosphorylation
Molecular Biology
Binding Sites
Cell growth
Kinase
fungi
Transfection
Phosphoproteins
Metabolic pathway
Phosphoglucomutase
p21-Activated Kinases
Biochemistry
Doxycycline
Signal Transduction
Subjects
Details
- ISSN :
- 14765594 and 09509232
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....747a3433fee4e5be0c7c3ba3ddd1b94d