Sökning: WFRF:(Scharfmann R) >
Imatinib mesilate-i...
-
Mokhtari, DariushUppsala universitet,Institutionen för medicinsk cellbiologi,Science for Life Laboratory, SciLifeLab
(författare)
Imatinib mesilate-induced phosphatidylinositol 3-kinase signalling and improved survival in insulin-producing cells : role of Src homology 2-containing inositol 5'-phosphatase interaction with c-Abl
- Artikel/kapitelEngelska2013
Förlag, utgivningsår, omfång ...
-
2013-03-05
-
Springer Science and Business Media LLC,2013
-
electronicrdacarrier
Nummerbeteckningar
-
LIBRIS-ID:oai:DiVA.org:uu-196342
-
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-196342URI
-
https://doi.org/10.1007/s00125-013-2868-2DOI
Kompletterande språkuppgifter
-
Språk:engelska
-
Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
-
Ämneskategori:ref swepub-contenttype
-
Ämneskategori:art swepub-publicationtype
Anmärkningar
-
AIMS/HYPOTHESIS: It is not clear how small tyrosine kinase inhibitors, such as imatinib mesilate, protect against diabetes and beta cell death. The aim of this study was to determine whether imatinib, as compared with the non-cAbl-inhibitor sunitinib, affects pro-survival signalling events in the phosphatidylinositol 3-kinase (PI3K) pathway. METHODS: Human EndoC-βH1 cells, murine beta TC-6 cells and human pancreatic islets were used for immunoblot analysis of insulin receptor substrate (IRS)-1, Akt and extracellular signal-regulated kinase (ERK) phosphorylation. Phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] plasma membrane concentrations were assessed in EndoC-βH1 and MIN6 cells using evanescent wave microscopy. Src homology 2-containing inositol 5'-phosphatase 2 (SHIP2) tyrosine phosphorylation and phosphatase and tensin homologue deleted on chromosome 10 (PTEN) serine phosphorylation, as well as c-Abl co-localisation with SHIP2, were studied in HEK293 and EndoC-βH1 cells by immunoprecipitation and immunoblot analysis. Gene expression was assessed using RT-PCR. Cell viability was measured using vital staining. RESULTS: Imatinib stimulated ERK(thr202/tyr204) phosphorylation in a c-Abl-dependent manner. Imatinib, but not sunitinib, also stimulated IRS-1(tyr612), Akt(ser473) and Akt(thr308) phosphorylation. This effect was paralleled by oscillatory bursts in plasma membrane PI(3,4,5)P3 levels. Wortmannin induced a decrease in PI(3,4,5)P3 levels, which was slower in imatinib-treated cells than in control cells, indicating an effect on PI(3,4,5)P3-degrading enzymes. In line with this, imatinib decreased the phosphorylation of SHIP2 but not of PTEN. c-Abl co-immunoprecipitated with SHIP2 and its binding to SHIP2 was largely reduced by imatinib but not by sunitinib. Imatinib increased total β-catenin levels and cell viability, whereas sunitinib exerted negative effects on cell viability. CONCLUSIONS/INTERPRETATION: Imatinib inhibition of c-Abl in beta cells decreases SHIP2 activity, which results in enhanced signalling downstream of PI3 kinase.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
-
Al-Amin, AbdullahUppsala universitet,Institutionen för medicinsk cellbiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)abdal875
(författare)
-
Turpaev, Kyrill
(författare)
-
Li, TingtingUppsala universitet,Institutionen för medicinsk cellbiologi,Science for Life Laboratory, SciLifeLab
(författare)
-
Idevall-Hagren, OlofUppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)olide169
(författare)
-
Li, JiaUppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)jiali219
(författare)
-
Wuttke, AnneUppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)annwu514
(författare)
-
Fred, Rikard GUppsala universitet,Institutionen för medicinsk cellbiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)rifre425
(författare)
-
Ravassard, Philippe
(författare)
-
Scharfmann, R
(författare)
-
Tengholm, AndersUppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)andeteng
(författare)
-
Welsh, NilsUppsala universitet,Institutionen för medicinsk cellbiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)nilswels
(författare)
-
Uppsala universitetInstitutionen för medicinsk cellbiologi
(creator_code:org_t)
Sammanhörande titlar
-
Ingår i:Diabetologia: Springer Science and Business Media LLC56:6, s. 1327-13380012-186X1432-0428
Internetlänk
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Mokhtari, Darius ...
-
Al-Amin, Abdulla ...
-
Turpaev, Kyrill
-
Li, Tingting
-
Idevall-Hagren, ...
-
Li, Jia
-
visa fler...
-
Wuttke, Anne
-
Fred, Rikard G
-
Ravassard, Phili ...
-
Scharfmann, R
-
Tengholm, Anders
-
Welsh, Nils
-
visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Medicinska och f ...
-
och Cell och molekyl ...
- Artiklar i publikationen
-
Diabetologia
- Av lärosätet
-
Uppsala universitet