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Tensin2 reduces intracellular phosphatidylinositol 3,4,5-trisphosphate levels at the plasma membrane.

Hafizi, Sassan LU ; Gustafsson, Anna LU ; Oslakovic, Cecilia LU ; Idevall-Hagren, Olof ; Tengholm, Anders ; Sperandio, Olivier ; Villoutreix, Bruno O and Dahlbäck, Björn LU (2010) In Biochemical and Biophysical Research Communications 399(3). p.396-401
Abstract
Tensins are proposed cytoskeleton-regulating proteins. However, Tensin2 additionally inhibits Akt signalling and cell survival. Structural modelling of the Tensin2 phosphatase (PTPase) domain revealed an active site-like pocket receptive towards phosphoinositides. Tensin2-expressing HEK293 cells displayed negligible levels of plasma membrane phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3)) under confocal microscopy. However, mock-transfected cells, and Tensin2 cells harbouring a putative phosphatase-inactivating mutation, exhibited significant PtdIns(3,4,5)P(3) levels, which decreased upon phosphatidylinositol 3-kinase inhibition with LY294002. In contrast, wtTensin3, mock and mutant cells were identical in membrane... (More)
Tensins are proposed cytoskeleton-regulating proteins. However, Tensin2 additionally inhibits Akt signalling and cell survival. Structural modelling of the Tensin2 phosphatase (PTPase) domain revealed an active site-like pocket receptive towards phosphoinositides. Tensin2-expressing HEK293 cells displayed negligible levels of plasma membrane phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3)) under confocal microscopy. However, mock-transfected cells, and Tensin2 cells harbouring a putative phosphatase-inactivating mutation, exhibited significant PtdIns(3,4,5)P(3) levels, which decreased upon phosphatidylinositol 3-kinase inhibition with LY294002. In contrast, wtTensin3, mock and mutant cells were identical in membrane PtdIns(3,4,5)P(3) and Akt phosphorylation. In vitro lipid PTPase activity was however undetectable in isolated recombinant PTPase domains of both Tensins, indicating a possible loss of structural stability when expressed in isolation. In summary, we provide evidence that Tensin2, in addition to regulating cytoskeletal dynamics, influences phosphoinositide-Akt signalling through its PTPase domain. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biochemical and Biophysical Research Communications
volume
399
issue
3
pages
396 - 401
publisher
Elsevier
external identifiers
  • wos:000281587400015
  • pmid:20678486
  • scopus:77956180303
ISSN
1090-2104
DOI
10.1016/j.bbrc.2010.07.085
language
English
LU publication?
yes
id
383270c3-147b-457b-8fbd-8ecf10ccf662 (old id 1665696)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20678486?dopt=Abstract
date added to LUP
2016-04-04 09:16:48
date last changed
2022-01-29 17:06:14
@article{383270c3-147b-457b-8fbd-8ecf10ccf662,
  abstract     = {{Tensins are proposed cytoskeleton-regulating proteins. However, Tensin2 additionally inhibits Akt signalling and cell survival. Structural modelling of the Tensin2 phosphatase (PTPase) domain revealed an active site-like pocket receptive towards phosphoinositides. Tensin2-expressing HEK293 cells displayed negligible levels of plasma membrane phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3)) under confocal microscopy. However, mock-transfected cells, and Tensin2 cells harbouring a putative phosphatase-inactivating mutation, exhibited significant PtdIns(3,4,5)P(3) levels, which decreased upon phosphatidylinositol 3-kinase inhibition with LY294002. In contrast, wtTensin3, mock and mutant cells were identical in membrane PtdIns(3,4,5)P(3) and Akt phosphorylation. In vitro lipid PTPase activity was however undetectable in isolated recombinant PTPase domains of both Tensins, indicating a possible loss of structural stability when expressed in isolation. In summary, we provide evidence that Tensin2, in addition to regulating cytoskeletal dynamics, influences phosphoinositide-Akt signalling through its PTPase domain.}},
  author       = {{Hafizi, Sassan and Gustafsson, Anna and Oslakovic, Cecilia and Idevall-Hagren, Olof and Tengholm, Anders and Sperandio, Olivier and Villoutreix, Bruno O and Dahlbäck, Björn}},
  issn         = {{1090-2104}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{396--401}},
  publisher    = {{Elsevier}},
  series       = {{Biochemical and Biophysical Research Communications}},
  title        = {{Tensin2 reduces intracellular phosphatidylinositol 3,4,5-trisphosphate levels at the plasma membrane.}},
  url          = {{http://dx.doi.org/10.1016/j.bbrc.2010.07.085}},
  doi          = {{10.1016/j.bbrc.2010.07.085}},
  volume       = {{399}},
  year         = {{2010}},
}