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Advances in Hematology
Volume 2012 (2012), Article ID 380635, 10 pages
http://dx.doi.org/10.1155/2012/380635
Review Article

Gab Adapter Proteins as Therapeutic Targets for Hematologic Disease

1Aflac Cancer Center of Children's Healthcare of Atlanta, Department of Pediatrics, Emory University, Atlanta, GA 30322, USA
2Aflac Cancer Center and Blood Disorders Service, Division of Hematology-Oncology, Department of Pediatrics, Emory University School of Medicine, 2015 Uppergate Drive NE, ECC 444, Atlanta, GA 30322, USA

Received 14 June 2011; Revised 30 August 2011; Accepted 6 September 2011

Academic Editor: Cheng-Kui Qu

Copyright © 2012 Sheetal Verma et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The Grb-2 associated binder (Gab) family of scaffolding/adaptor/docking proteins is a group of three molecules with significant roles in cytokine receptor signaling. Gabs possess structural motifs for phosphorylation-dependent receptor recruitment, Grb2 binding, and activation of downstream signaling pathways through p85 and SHP-2. In addition, Gabs participate in hematopoiesis and regulation of immune response which can be aberrantly activated in cancer and inflammation. The multifunctionality of Gab adapters might suggest that they would be too difficult to consider as candidates for “targeted” therapy. However, the one drug/one target approach is giving way to the concept of one drug/multiple target approach since few cancers are addicted to a single signaling molecule for survival and combination drug therapies can be problematic. In this paper, we cover recent findings on Gab multi-functionality, binding partners, and their role in hematological malignancy and examine the concept of Gab-targeted therapy.