Quantitative proteome analysis of detergent-resistant membranes identifies the differential regulation of protein kinase C isoforms in apoptotic T cells

Solstad, T; Bjørgo, E; Koehler, CJ; Strozynski, M; Torgersen, KM; Taskén, K; Thiede, B

HERO ID

1055762

Reference Type

Journal Article

Year

2010

Language

English

PMID

20486122

HERO ID 1055762
In Press No
Year 2010
Title Quantitative proteome analysis of detergent-resistant membranes identifies the differential regulation of protein kinase C isoforms in apoptotic T cells
Authors Solstad, T; Bjørgo, E; Koehler, CJ; Strozynski, M; Torgersen, KM; Taskén, K; Thiede, B
Journal Proteomics
Volume 10
Issue 15
Page Numbers 2758-2768
Abstract Several lines of evidence suggest that detergent-resistant membranes (DRMs) (also known as lipid rafts and glycosphingolipid-enriched microdomains) may have a role in signaling pathways of apoptosis. Here, we developed a method that combines DRMs isolation and methanol/chloroform extraction with stable isotope labeling with amino acids in cell culture-based quantitative proteome analysis of DRMs from control and cisplatin-induced apoptotic Jurkat T cells. This approach enabled us to enrich proteins with a pivotal role in cell signaling of which several were found with increased or decreased amounts in DRMs upon induction of apoptosis. Specifically, we show that three isoforms of protein kinase C (PKC) are regulated differently upon apoptosis. Although PKC alpha which belongs to the group of conventional PKCs is highly up-regulated in DRMs, the levels of two novel PKCs, PKC eta and PKC theta, are significantly reduced. These alterations/differences in PKC regulation are verified by immunoblotting and confocal microscopy. In addition, a specific enrichment of PKC alpha in apoptotic blebs and buds is shown. Furthermore, we observe an increased expression of ecto-PKC alpha as a result of exposure to cisplatin using flow cytometry. Our results demonstrate that in-depth proteomic analysis of DRMs provides a tool to study differential localization and regulation of signaling molecules important in health and disease.
Doi 10.1002/pmic.201000164
Pmid 20486122
Wosid WOS:000281054300003
Is Certified Translation No
Dupe Override No
Comments Source: Web of Science 000281054300003
Is Public Yes
Language Text English
Keyword Apoptosis; Cell biology; Detergent-resistant membranes; Lipid rafts; Protein kinase C; Quantitative proteomics
Is Qa No