Inhibition of glycogen phosphorylation induces changes in cellular proteome and signaling pathways in MIA pancreatic cancer cells

Danjun Ma, Jiarui Wang, Yingchun Zhao, Wai Nang Paul Lee, Jing Xiao, Vay Liang W Go, Qi Wang, Robert R. Recker, Gary Guishan Xiao

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

OBJECTIVES: Novel quantitative proteomic approaches were used to study the effects of inhibition of glycogen phosphorylase on proteome and signaling pathways in MIA PaCa-2 pancreatic cancer cells. METHODS: We performed quantitative proteomic analysis in MIA PaCa-2 cancer cells treated with a stratified dose of CP-320626 (5-chloro-1H-indole-2-carboxylic acid [1-(4-fuorobenzyl)-2-(4-hydroxypiperidin-1-yl)-2 oxoethyl] amide) (25, 50, and 100 μM). The effect of metabolic inhibition on cellular protein turnover dynamics was also studied using the modified SILAC (stable isotope labeling with amino acids in cell culture) method. RESULTS: A total of 22 protein spots and 4 phosphoprotein spots were quantitatively analyzed. We found that dynamic expression of total proteins and phosphoproteins was significantly changed in MIA PaCa-2 cells treated with an incremental dose of CP-320626. Functional analyses suggested that most of the proteins differentially expressed were in the pathways of mitogen-activated protein kinase/extracellular signal-regulated kinase and tumor necrosis factor α/nuclear factor κB. CONCLUSIONS: Signaling pathways and metabolic pathways share many common cofactors and substrates forming an extended metabolic network. The restriction of substrate through 1 pathway such as inhibition of glycogen phosphorylation induces pervasive metabolomic and proteomic changes manifested in protein synthesis, breakdown, and posttranslational modification of signaling molecules. Our results suggest that quantitative proteomic is an important approach to understand the interaction between metabolism and signaling pathways.

Original languageEnglish
Pages (from-to)397-408
Number of pages12
JournalPancreas
Volume41
Issue number3
DOIs
StatePublished - Apr 2012

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Proteome
Glycogen
Pancreatic Neoplasms
Proteomics
Phosphorylation
Phosphoproteins
Metabolic Networks and Pathways
Proteins
Isotope Labeling
Glycogen Phosphorylase
Metabolomics
Extracellular Signal-Regulated MAP Kinases
Post Translational Protein Processing
Mitogen-Activated Protein Kinases
Amides
Cell Culture Techniques
Tumor Necrosis Factor-alpha
Amino Acids
Neoplasms
CP 320626

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Internal Medicine
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Inhibition of glycogen phosphorylation induces changes in cellular proteome and signaling pathways in MIA pancreatic cancer cells. / Ma, Danjun; Wang, Jiarui; Zhao, Yingchun; Lee, Wai Nang Paul; Xiao, Jing; Go, Vay Liang W; Wang, Qi; Recker, Robert R.; Xiao, Gary Guishan.

In: Pancreas, Vol. 41, No. 3, 04.2012, p. 397-408.

Research output: Contribution to journalArticle

Ma, Danjun ; Wang, Jiarui ; Zhao, Yingchun ; Lee, Wai Nang Paul ; Xiao, Jing ; Go, Vay Liang W ; Wang, Qi ; Recker, Robert R. ; Xiao, Gary Guishan. / Inhibition of glycogen phosphorylation induces changes in cellular proteome and signaling pathways in MIA pancreatic cancer cells. In: Pancreas. 2012 ; Vol. 41, No. 3. pp. 397-408.
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