| 1. |
- Alvarado-Kristensson, Maria, et al.
(författare)
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SADB phosphorylation of gamma-tubulin regulates centrosome duplication.
- 2009
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Ingår i: Nature Cell Biology. - : Springer Science and Business Media LLC. - 1465-7392 .- 1476-4679. ; 11:9, s. 86-1081
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Tidskriftsartikel (refereegranskat)abstract
- Symmetrical cell division requires duplication of DNA and protein content to generate two daughter cells. Centrosomes also duplicate during cell division, but the mechanism controlling this process is incompletely understood. We describe an alternative splice form of SadB encoding a short SADB Ser/Thr kinase whose activity fluctuates during the cell cycle, localizes to centrosomes, and controls centrosome duplication. Reduction of endogenous SADB levels diminished centrosome numbers, whereas enhanced SADB expression induced centrosome amplification. SADB exerted this action through phosphorylation of gamma-tubulin on Ser 131, as expression of a phosphomimetic Ser 131-to-Asp gamma-tubulin mutant alone increased centrosome numbers, whereas non-phosphorylatable Ala 131-gamma-tubulin impaired centrosome duplication. We propose that SADB kinase activity controls centrosome homeostasis by regulating phosphorylation of gamma-tubulin.
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| 2. |
- Alvarado-Kristensson, Maria, et al.
(författare)
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Protein phosphatase 2A regulates apoptosis in neutrophils by dephosphorylating both p38 MAPK and its substrate caspase 3.
- 2005
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 280:7, s. 6238-6244
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Tidskriftsartikel (refereegranskat)abstract
- The induction of apoptosis in neutrophils is an essential event in the resolution of an inflammatory process. We found recently that the reduction of the activity of the neutrophil survival factor p38 MAPK and dephosphorylation and thus activation of caspases must occur to initiate such cell death in these leukocytes. Here, we report a previously undetected early and transient activation of protein phosphatase 2A WPM in neutrophils undergoing apoptosis. The pharmacological inhibition of this phosphatase during Fas-induced apoptosis augmented the levels of phosphorylation of both p38 MAPK and caspase 3, resulting in a decreased activity of caspase 3 and an increased neutrophil survival. The complementary finding of a time-dependent association among PP2A, p38 MAPK, and caspase 3 in intact neutrophils indicated that there is a direct regulatory link among these signaling enzymes during Fas-provoked apoptosis. Moreover, immunoprecipitated active p38 MAPK and recombinant phosphorylated caspase 3 were dephosphorylated by exposure to purified PP2A in vitro. Consequently, the early and temporary activation of PP2A in neutrophils impaired not only the p38 MAPK-mediated inhibition of caspase 3 but also restored the activity to caspase 3 that had already been phosphorylated and thereby inactivated. These findings indicate that PP2A plays a pivotal dual role in the induction of neutrophil apoptosis and therefore also in the resolution of inflammation.
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| 3. |
- Barber, D F, et al.
(författare)
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PTEN regulation, a novel function for the p85 subunit of phosphoinositide 3-kinase
- 2006
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Ingår i: Science Signaling. - 1937-9145. ; 362, s. 49-49
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Tidskriftsartikel (refereegranskat)abstract
- Timely regulation of phosphatidylinositol-3,4-bisphosphate [PI(3,4)P2] and phosphatidylinositol-3,4,5-trisphosphate [PI(3,4,5)P3] abundance in cells is essential for the control of cellular homeostasis. The concentrations of these lipids are low in quiescent cells but rapidly and transiently increase following growth factor receptor (GFR) stimulation, which triggers cellular metabolic changes, proliferation, survival, and motility. Class I(A) phosphatidylinositol 3-kinase (PI3K), which is composed of a p85 (regulatory) and p110 (catalytic) subunits, is the enzyme generating PI(3,4)P2 and PI(3,4,5)P3 following GFR stimulation. Although the steps in GFR-induced activation of PI3K , are relatively well known, the mechanisms for subsequent 3-polyphospho-PI down-regulation are less understood. Examination of frequent genetic alterations in human cancer showed that PTEN (phosphatase with tensin homology on chromosome 10) is the major enzyme that decreases PI(3,4)P2 and PI(3,4,5)P3 cell content. Nonetheless, interpretation of the complexity of PTEN regulation remains a matter of debate. The recent description of diminished PTEN activity in liver-conditional knockout mice lacking the p85alpha PI3K regulatory subunit reveals a previously unknown p85alpha-dependent negative-feedback pathway that controls PI(3,4)P2 and PI(3,4,5)P3 half-life by regulating PTEN.
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| 4. |
- Carrera, Ana, et al.
(författare)
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SADB kinases license centrosome replication
- 2009
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Ingår i: Cell Cycle. - : Informa UK Limited. - 1551-4005 .- 1538-4101. ; 8:24, s. 4005-4006
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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