Akt, a target of phosphatidylinositol 3-kinase, inhibits apoptosis in a differentiating neuronal cell line

EM Eves, W Xiong, A Bellacosa… - … and cellular biology, 1998 - Taylor & Francis
EM Eves, W Xiong, A Bellacosa, SG Kennedy, PN Tsichlis, MR Rosner, N Hay
Molecular and cellular biology, 1998Taylor & Francis
ABSTRACT Phosphatidylinositol (PI) 3-kinase has been suggested to mediate cell survival.
Consistent with this possibility, apoptosis of conditionally (simian virus 40 Tts) immortalized
rat hippocampal H19-7 neuronal cells was increased in response to wortmannin, an
inhibitor of PI 3-kinase. Downstream effectors of PI 3-kinase include Rac1, protein kinase C,
and the serine-threonine kinase Akt (protein kinase B). Here, we show that activation of Akt
is one mechanism by which PI 3-kinase can mediate survival of H19-7 cells during serum …
Abstract
Phosphatidylinositol (PI) 3-kinase has been suggested to mediate cell survival. Consistent with this possibility, apoptosis of conditionally (simian virus 40 Tts) immortalized rat hippocampal H19-7 neuronal cells was increased in response to wortmannin, an inhibitor of PI 3-kinase. Downstream effectors of PI 3-kinase include Rac1, protein kinase C, and the serine-threonine kinase Akt (protein kinase B). Here, we show that activation of Akt is one mechanism by which PI 3-kinase can mediate survival of H19-7 cells during serum deprivation or differentiation. While ectopic expression of wild-type Akt (c-Akt) does not significantly enhance survival in H19-7 cells, expression of activated forms of Akt (v-Akt or myristoylated Akt) results in enhanced survival which can be comparable to that conferred by Bcl-2. Conversely, expression of a dominant-negative mutant of Akt accelerates cell death upon serum deprivation or differentiation. Finally, the results indicate that Akt can transduce a survival signal for differentiating neuronal cells through a mechanism that is independent of induction of Bcl-2 or Bcl-xL or inhibition of Jun kinase activity.
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