Review

Function, regulation and pathological roles of the Gab/DOS docking proteins

Franziska U Wöhrle^1,2,3 , Roger J Daly^4,5 and Tilman Brummer^2,3,6

¹  Spemann Graduate School of Biology and Medicine, Albert-Ludwigs-University of Freiburg, Germany

²  Centre for Biological Systems Analysis (ZBSA), Albert-Ludwigs-University of Freiburg, Germany

³  Institute for Biology III, Albert-Ludwigs-University of Freiburg, Germany

⁴  Cancer Research Program, The Garvan Institute of Medical Research, Australia

⁵  St Vincent's Clinical School, University of New South Wales, Australia

⁶  Centre for Biological Signalling studies (bioss), Albert-Ludwigs-University of Freiburg, Germany

author email corresponding author email

Cell Communication and Signaling 2009, 7:22doi:10.1186/1478-811X-7-22

Published:	8 September 2009

Abstract

Since their discovery a little more than a decade ago, the docking proteins of the Gab/DOS family have emerged as important signalling elements in metazoans. Gab/DOS proteins integrate and amplify signals from a wide variety of sources including growth factor, cytokine and antigen receptors as well as cell adhesion molecules. They also contribute to signal diversification by channelling the information from activated receptors into signalling pathways with distinct biological functions. Recent approaches in protein biochemistry and systems biology have revealed that Gab proteins are subject to complex regulation by feed-forward and feedback phosphorylation events as well as protein-protein interactions. Thus, Gab/DOS docking proteins are at the centre of entire signalling subsystems and fulfil an important if not essential role in many physiological processes. Furthermore, aberrant signalling by Gab proteins has been increasingly linked to human diseases from various forms of neoplasia to Alzheimer's disease.

In this review, we provide a detailed overview of the structure, effector functions, regulation and evolution of the Gab/DOS family. We also summarize recent findings implicating Gab proteins, in particular the Gab2 isoform, in leukaemia, solid tumours and other human diseases.