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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • Sassan Hafizi
  • Anna Gustafsson
  • Cecilia Oslakovic
  • Olof Idevall-Hagren
  • Anders Tengholm
  • Olivier Sperandio
  • Bruno O Villoutreix
  • Björn Dahlbäck
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Biologiska vetenskaper
Originalspråkengelska
Sidor (från-till)396-401
TidskriftBiochemical and Biophysical Research Communications
Volym399
Utgivningsnummer3
StatusPublished - 2010
PublikationskategoriForskning
Peer review utfördJa