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Signaling Pathway Initiated By Nuclear Localized PDK1 Promotes Cell Survival And Proliferation
Author(s) -
Kikani Chintan K,
Dong Lily Q,
Liu Feng
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1035-a
Subject(s) - pten , nuclear localization sequence , protein kinase b , microbiology and biotechnology , cell growth , nuclear protein , signal transduction , nuclear export signal , activator (genetics) , biology , chemistry , cell nucleus , pi3k/akt/mtor pathway , cancer research , cytoplasm , transcription factor , biochemistry , gene
We have recently found that phosphoinositide‐dependent kinase 1 (PDK1), a kinase functioning downstream of PI‐3K and activator of Akt, is a nucleo‐cytoplasmic shuttling protein. Additionally, loss of PTEN tumor suppressor increases nuclear localization of PDK1. In order to elucidate the functions of nuclear PDK1, we generated mouse embryonic fibroblast cells stably expressing WT or constitutively nuclear‐localized PDK1. Interestingly, nuclear PDK1 expressing cells demonstrated higher prolieration rate and an accelerated G1‐S phase transition compared to WT PDK1 expressing cell lines. Nuclear PDK1 cell lines also demonstrated decreased TNF‐α stimulated caspase‐3 and stress activated MAP kinase activation. These results suggest that nuclear localized PDK1 participates in anti‐apoptotic signaling. Furthermore, nuclear PDK1 expressing cells prolonged the presence of activated AKT in the nucleus. Finally, we demonstrate that many tumor derived cell lines with aggressive metastatic potential and cell proliferation demonstrated elevated PDK1 nuclear localization, indicating that the nuclear localization of PDK1, as observed in cells lacking PTEN, may promote oncogenic signaling.