Akt signaling dynamics in plasma membrane microdomains visualized by FRET-based reporters.
Human kinase Akt has been shown to be activated at the plasma membrane upon generation of the cell membrane bound second messenger phosphatidylinositol (3,4,5)-trisphosphate through phosphatidylinositol 3-kinase (PI3K). Several components in the PI3K/Akt signaling pathway have been found in the detergent-resistant plasma membrane compartments, lipid rafts. Increasing evidence also suggests crucial roles of lipid rafts in the activation of Akt in different cell types. However, the regulatory mechanisms of Akt activation at different microdomains of the plasma membrane are not clear. Using a newly developed genetically encodable fluorescent kinase reporter based on fluorescence resonance energy transfer (FRET), AktAR, we studied spatio-temporal dynamics of Akt activity within plasma membrane microdomains in live-cell context. Our studies suggest that Akt activity is turned on more rapidly in lipid rafts upon growth factor stimulation, and platelet-derived growth factor (PDGF) or insulin-like Growth Factor-1 (IGF-1) stimulated Akt activity is differentially regulated between raft and non-raft regions of the plasma membrane.
Gao
Xinxin
X
Department of Pharmacology and Molecular Sciences; and The Solomon H. Snyder Department of Neuroscience and Department of Oncology; The Johns Hopkins University School of Medicine; Baltimore, Maryland USA.
Zhang
Jin
J
Cell Signal. 2007 May;19(5):1081-92
17275257
Proc Natl Acad Sci U S A. 2005 Oct 18;102(42):15081-6
16214892
Trends Biochem Sci. 2001 Nov;26(11):657-64
11701324
Cancer Res. 2007 Jul 1;67(13):6238-46
17616681
Science. 1991 Oct 11;254(5029):274-7
1833819
J Cell Sci. 2005 Dec 15;118(Pt 24):5675-8
16339964
Proc Natl Acad Sci U S A. 1991 May 15;88(10):4171-5
1851997
Exp Cell Res. 2004 May 1;295(2):512-24
15093748
J Cell Sci. 2000 Jan;113 Pt 2:207-14
10633072
Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14950-5
9843996
Science. 2005 Apr 1;308(5718):114-8
15802604
Nat Rev Drug Discov. 2007 Oct;6(10):821-33
17906644
Nat Chem Biol. 2008 Sep;4(9):538-47
18641634
Mol Biol Cell. 2008 Oct;19(10):4366-73
18701703
Nat Clin Pract Oncol. 2005 Feb;2(2):82-9
16264880
Cell. 2007 Jun 29;129(7):1261-74
17604717
Mayo Clin Proc. 2006 Sep;81(9):1241-57
16970222