Comprehensive Identification of PIP3-Regulated PH Domains from C. elegans to H. sapiens by Model Prediction and Live Imaging

101Citations
Citations of this article
109Readers
Mendeley users who have this article in their library.

Abstract

Phosphoinositide 3-kinase (PI3K) and its product phosphatidylinositol(3,4,5)-trisphosphate (PIP3) control cell growth, migration, and other processes by recruiting proteins with pleckstrin homology (PH) domains and possibly other domains to the plasma membrane (PM). However, previous experimental and structural work with PH domains left conflicting evidence about which ones are PIP3 regulated. Here we used live-cell confocal imaging of 130 YFP-conjugated mouse PH domains and found that 20% translocated to the PM in response to receptor-generated PIP3 production. We developed a recursive-learning algorithm to predict PIP3 regulation of 1200 PH domains from different eukaryotes and validated that it accurately predicts PIP3 regulation. Strikingly, this algorithm showed that PIP3 regulation is specified by amino acids across the PH domain, not just the PIP3-binding pocket, and must have evolved several times independently from PIP3-insensitive ancestral PH domains. Finally, our algorithm and live-cell experiments provide a functional survey of PH domains in different species, showing that PI3K regulation increased from approximately two C. elegans and four Drosophila to 40 vertebrate proteins. © 2008 Elsevier Inc. All rights reserved.

Author supplied keywords

Cite

CITATION STYLE

APA

Park, W. S., Do Heo, W., Whalen, J. H., O’Rourke, N. A., Bryan, H. M., Meyer, T., & Teruel, M. N. (2008). Comprehensive Identification of PIP3-Regulated PH Domains from C. elegans to H. sapiens by Model Prediction and Live Imaging. Molecular Cell, 30(3), 381–392. https://doi.org/10.1016/j.molcel.2008.04.008

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free