Vimentin is a novel RPTPβ binding partner mediating IGF-I signaling and biological actions

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 389-405-Signaling Originating from Membrane Receptors
Basic/Translational
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-389
Xinchun Shen*, Gang Xi, Christine Wai and David R Clemmons
University of North Carolina at Chapel Hill, Chapel Hill, NC
Insulin-like growth factor binding protein-2 (IGFBP-2) functions coordinately with receptor protein tyrosine phosphatase β (RPTPβ) and the IGF-I receptor to regulate IGF-I-stimulated AKT activation and that this is mediated through inhibition of RPTPβ mediated PTEN dephosphorylation. Our previous studies showed that IGFBP-2 binding to RPTPβ alone was not adequate to stimulate RPTPβ dimerization (required for inhibition of its phosphatase activity and AKT activation) and this also required IGF-I. Inhibition of IGF-I binding to IGFBP-2 had no effect whereas inhibition of IGF-I receptor tyrosine kinase effectively inhibited RPTPβ dimerization. However, the mechanism by which stimulation of the IGF-I receptor led to RPTPβ inactivation was unclear. In the present study, employing a proteomics screening approach, vimentin was found to bind directly to RPTPβ in response to IGF-I. Coimmunoprecipitation studies showed that IGF-I directly stimulated PRTPβ /vimentin association. Our results showed that IGF-I stimulated serine phosphorylation of vimentin. Since serine phosphorylation of vimentin has been shown the essential for its binding to other proteins, this suggests that IGF-I stimulated RPTPβ/vimentin association could be mediated by this phosphorylation. Further experiments showed that inhibition of IGF-I stimulated PI-3 kinase activation disrupted  RPTPβ/vimentin association. Since vimetin binding to phosphatases has been shown to inhibit their activity vimentin binding to RPTPβ represents an excellent candidate for mediating this response. We conclude that vimentin is a novel RPTPβ binding partner which could mediate IGF-I-dependent activation of RPTPβ/PTEN/AKT pathway thereby leading to enhancement of IGF-I signaling and biological actions.

Nothing to Disclose: XS, GX, CW, DRC

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Previous Abstract | Next Abstract >>