A cell model system to study regulation of phosphotidylinositol 3-kinase and protein kinase B activity by cytokines/growth factors produced by type I collagen stimulated immune cells from patients with systemic sclerosis

Thomas M. Chiang, Arnold Postlethwaite

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5 Citations (Scopus)

Abstract

We have reported that posttranslational modification of systemic sclerosis patients' platelet phosphoinositide 1,3,4,5 kinase (PI 3-K) and protein kinase B (Akt) altered their enzymatic activities. In the present investigation, we have established a cell line model to study further the effects of posttranslational modification and modification by cytokines or growth factors of these two enzymes. Results from these studies suggest that posttranslational modification by phosphorylation of Akt and nitrotyrosylation of PI 3-K increases enzymatic activities, as was observed from SSc patients' platelets. These two signaling components are controlled by a different mechanism, which alters platelet reactivity towards the matrix components of vascular walls. We have used a megakaryotic cell line to study these two enzymes in the presence of cultured supernatants from peripheral blood mononuclear cells (PBMC), which were isolated from blood of SSc patients compared to controls including culture medium, rheumatoid arthritis, systemic lupus erythematosus, and osteoarthritis. The effect of the supernatants from SSc CI-stimulated PBMC cultures on both PI 3-K and Akt is specific.

Original languageEnglish (US)
Pages (from-to)1181-1186
Number of pages6
JournalBiochimica et Biophysica Acta - General Subjects
Volume1770
Issue number8
DOIs
StatePublished - Aug 1 2007

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Proto-Oncogene Proteins c-akt
Systemic Scleroderma
Post Translational Protein Processing
Collagen Type I
Platelets
Phosphatidylinositols
Intercellular Signaling Peptides and Proteins
Blood
Phosphotransferases
Blood Platelets
Cytokines
Blood Cells
Cells
Cell Line
Phosphorylation
Enzymes
Cell culture
Osteoarthritis
Systemic Lupus Erythematosus
Blood Vessels

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

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title = "A cell model system to study regulation of phosphotidylinositol 3-kinase and protein kinase B activity by cytokines/growth factors produced by type I collagen stimulated immune cells from patients with systemic sclerosis",
abstract = "We have reported that posttranslational modification of systemic sclerosis patients' platelet phosphoinositide 1,3,4,5 kinase (PI 3-K) and protein kinase B (Akt) altered their enzymatic activities. In the present investigation, we have established a cell line model to study further the effects of posttranslational modification and modification by cytokines or growth factors of these two enzymes. Results from these studies suggest that posttranslational modification by phosphorylation of Akt and nitrotyrosylation of PI 3-K increases enzymatic activities, as was observed from SSc patients' platelets. These two signaling components are controlled by a different mechanism, which alters platelet reactivity towards the matrix components of vascular walls. We have used a megakaryotic cell line to study these two enzymes in the presence of cultured supernatants from peripheral blood mononuclear cells (PBMC), which were isolated from blood of SSc patients compared to controls including culture medium, rheumatoid arthritis, systemic lupus erythematosus, and osteoarthritis. The effect of the supernatants from SSc CI-stimulated PBMC cultures on both PI 3-K and Akt is specific.",
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AU - Postlethwaite, Arnold

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AB - We have reported that posttranslational modification of systemic sclerosis patients' platelet phosphoinositide 1,3,4,5 kinase (PI 3-K) and protein kinase B (Akt) altered their enzymatic activities. In the present investigation, we have established a cell line model to study further the effects of posttranslational modification and modification by cytokines or growth factors of these two enzymes. Results from these studies suggest that posttranslational modification by phosphorylation of Akt and nitrotyrosylation of PI 3-K increases enzymatic activities, as was observed from SSc patients' platelets. These two signaling components are controlled by a different mechanism, which alters platelet reactivity towards the matrix components of vascular walls. We have used a megakaryotic cell line to study these two enzymes in the presence of cultured supernatants from peripheral blood mononuclear cells (PBMC), which were isolated from blood of SSc patients compared to controls including culture medium, rheumatoid arthritis, systemic lupus erythematosus, and osteoarthritis. The effect of the supernatants from SSc CI-stimulated PBMC cultures on both PI 3-K and Akt is specific.

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