The docking protein and proto-oncogene product Gab2 is regulated via a novel negative feedback mechanism mediated by 14-
- PDF / 97,255 Bytes
- 2 Pages / 610 x 792 pts Page_size
- 90 Downloads / 151 Views
BioMed Central
Open Access
Meeting abstract
The docking protein and proto-oncogene product Gab2 is regulated via a novel negative feedback mechanism mediated by 14-3-3 binding T Brummer*1, M Larance2, MT Herrera Abreu1, RJ Lyons1, P Timpson1, CH Emmerich1, EDG Fleuren1, GM Lehrbach1, D Schramek4, M Guilhaus3, DE James2 and RJ Daly1 Address: 1Cancer Research Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia, 2Diabetes and Obesity Research, Garvan Institute of Medical Research, Sydney, New South Wales, Australia, 3Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, Australia and 4Institute of Molecular Biotechnology, Vienna, Austria * Corresponding author
from 12th Joint Meeting of the Signal Transduction Society (STS). Signal Transduction: Receptors, Mediators and Genes Weimar, Germany. 29–31 October 2008 Published: 26 February 2009 Cell Communication and Signaling 2009, 7(Suppl 1):A12
doi:10.1186/1478-811X-7-S1-A12
12th Joint Meeting of the Signal Transduction Society (STS). Signal Transduction: Receptors, Mediators and Genes
Frank Entschladen, Karlheinz Friedrich, Ralf Hass and Ottmar Janssen Meeting abstracts – A single PDF containing all abstracts in this Supplement is available here.This abstract is available from: http://www.biosignaling.com/content/7/S1/A12 © 2009 Brummer et al; licensee BioMed Central Ltd.
In vertebrates, Grb2-associated binder (Gab)1–3 constitute a family of conserved docking proteins. Gab2 is tyrosine-phosphorylated upon activation of a variety of growth factor, hormone, antigen, cytokine and cell matrix receptors, leading to the recruitment of specific src homology (SH)2 domain-containing effectors, which include the p85 subunit of phosphatidylinositol (PI)3-kinase and the protein tyrosine phosphatase Shp2. These Gab2 effectors potentiate the activation of the PI3-K/AKT and Ras/ ERK pathways, respectively. Studies using gene knock-out mice indicate that Gab2 is required for normal mast cellmediated allergic responses and osteoclast differentiation, and in combination with Gab1, for cardiac function. In addition, Gab2 signals downstream of several oncogenic tyrosine kinases, and are overexpressed in breast cancer, and promotes erbB2-induced mammary tumourigenesis. Therefore, it is critical to define how Gab2 signalling is regulated in normal and pathological states. One critical event in Gab2 signalling is its interaction with the adaptor protein Grb2, which promotes its association with specific receptors and thereby sustains its tyrosine phosphorylation dependent recruitment of the aforementioned effectors. However, the molecular mechanisms that attenuate or limit Gab2 signals have remained unclear.
In the presented study, we have addressed Gab2 regulation using an integrated approach that combines a proteomics-based definition of the Gab2 'phosphomap" with bioinformatics, biochemistry and cell biology. Here we report the discovery of 21 novel phosphorylation sites on human Gab2. Furthermore, we demonstrate t
Data Loading...
