Signal propagation from membrane messengers to nuclear effectors revealed by reporters of phosphoinositide dynamics and Akt activity.

ABSTRACT: Among various second messengers, phosphatidylinositol 3,4,5-triphosphate (PIP3) and phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2] regulate a variety of cellular processes, such as cell survival, polarization, and proliferation. Many of these functions are achieved via activation of serine/threonine kinase Akt. To investigate the spatiotemporal regulation of these lipids, we constructed a genetically targetable phosphoinositide (PI) indicator by sandwiching pleckstrin homology (PH) domain of Akt and a "pseudoligand" containing acidic amino acid residues, between cyan and yellow mutants of GFP. In living cells, elevations in PIP3 and PI(3,4)P2 by growth factor-induced activation of phosphatidylinositol 3-kinase (PI3K) resulted in a change in fluorescence resonance energy transfer (FRET)

SUBMITTER: Ananthanarayanan B 

PROVIDER: S-EPMC1257695 | biostudies-literature | 2005 Oct

REPOSITORIES: biostudies-literature