Abstract
Akt/PKB is a crucial regulator of diverse cellular processes and contributes to cancer progression. Activation of Akt is essentially dependent on phosphatidylinositol (PI) 3-kinase signaling. Here, we describe a novel mediator of Akt that is independent of PI 3-kinase. This mediator, PIKE-A, is a PIKE isoform and contains GTPase, pleckstrin homology, ArfGAP, and ankyrin repeats domains. PIKE-A directly binds to activated Akt but not PI 3-kinase in a guanine nucleotide-dependent way and stimulates the kinase activity of Akt. Overexpression of PIKE-A enhances Akt activity and promotes cancer cell invasion, whereas dominant-negative PIKE-A and PIKE-A knockdown markedly inhibit these processes. Our results demonstrate that PIKE-A is a physiologic regulator of Akt and an oncogenic effector of cell invasion.
Original language | English (US) |
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Pages (from-to) | 16441-16451 |
Number of pages | 11 |
Journal | Journal of Biological Chemistry |
Volume | 279 |
Issue number | 16 |
DOIs | |
State | Published - Apr 16 2004 |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology