磷脂酰肌醇
细胞生物学
磷酸酶
磷酸化
Pleckstrin同源结构域
磷脂酰肌醇4,5-二磷酸
蛋白激酶B
转染
细胞骨架
生物
化学
细胞培养
生物化学
细胞
遗传学
作者
Sassan Hafizi,Anna Gustafsson,Cecilia Oslakovic,Olof Idevall‐Hagren,Anders Tengholm,Olivier Spérandio,Bruno O. Villoutreix,Björn Dahlbäck
标识
DOI:10.1016/j.bbrc.2010.07.085
摘要
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.
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