GSBS Student Publications

Title

Isoform-specific regulation of Akt signaling by the endosomal protein WDFY2.

Student Author(s)

Xiarong Shi; Deanna M. Navaroli

UMMS Affiliation

Graduate School of Biomedical Sciences, Interdisciplinary Graduate Program; Program in Molecular Medicine

Date

5-7-2010

Document Type

Article

Medical Subject Headings

Intracellular Signaling Peptides and Proteins; Caenorhabditis elegans Proteins; Proto-Oncogene Proteins c-akt; Insulin; Glucose Transporter Type 4; Protein Isoforms

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Recent work has led to the identification of novel endocytic compartments with functional roles in both protein trafficking and growth factor signal transduction. The phosphatidylinositol 3-phosphate binding, FYVE domain-containing protein WDFY2 is localized to a distinct subset of early endosomes, which are localized close to the plasma membrane. Here, we find that the serine/threonine kinase Akt interacts with these endosomes in an isoform-specific manner. Using quantitative fluorescence microscopy we demonstrate specific co-localization of WDFY2 with endogenous Akt2, but not Akt1. Moreover, depletion of WDFY2 leads to impaired phosphorylation of Akt in response to insulin due to isoform specific reduction of Akt2, but not Akt1, protein levels, and to a marked reduction in the insulin-stimulated phosphorylation of numerous Akt substrates. This is accompanied by an impairment in insulin-stimulated glucose transport and, after prolonged silencing, a reduction in the level of expression of adipogenic genes. We propose that WDFY2-enriched endosomes serve as a scaffold that enables specificity of insulin signaling through Akt2.

Rights and Permissions

Citation: J Biol Chem. 2010 May 7;285(19):14101-8. Epub 2010 Feb 26.

Related Resources

Link to article in PubMed

Journal Title

The Journal of biological chemistry

PubMed ID

20189988