GAB gene familly

The GAB gene family (GAB stands for GRB2-associated binding protein) comprises a group of genes that encode intracellular adapter orscaffold proteins. These proteins mediate signal transduction from activated cell surface receptors to intracellular signaling pathways, thereby regulating cell proliferation, differentiation, migration, survival, and immune responses.

GAB proteins possess an N-terminal pleckstrin homology domain (PH domain), which facilitates their recruitment to the cell membrane, as well as numerous tyrosine phosphorylation sites. Upon activation of the corresponding receptors, they become phosphorylated and serve as a binding platform for other signaling molecules, particularly SHP2 and PI3K.

This primarily influences two signaling cascades:

1. RAS–RAF–MEK–ERK signaling pathway: Regulation of cell proliferation and differentiation.
2. PI3K–AKT–mTOR signaling pathway: Regulation of cell survival, cell growth, and metabolism.

Altered expression or activation of GAB proteins can contribute to the dysregulation of intracellular signaling pathways. GAB2, in particular, has been linked to various malignant diseases, including leukemias, breast cancer, and melanoma. Amplification or overexpression of GAB2 can enhance oncogenic signaling processes.

Dermatological significance: GAB1 and GAB2 are involved in the signaling of growth factors in epidermal and melanocyte cells . GAB2 can enhance PI3K–AKT signaling, particularly in melanoma, thereby promoting tumor progression and invasiveness. Furthermore, GAB2 plays a role in the activation of mast cells via the high-affinity IgE receptor FcεRI .

The GAB gene family should not be confused with GABA (γ-aminobutyric acid) or GABA receptors!

The GAB gene family does not encode receptors or independent enzymes, but rather intracellular signaling adaptors that consolidate various receptor signals and relay them to central regulatory signaling networks.

1. Abbeyquaye T et al. (2003) Evolution of Gab family adaptor proteins. Gene 311:43–50.
2. Kramer MH et al. (2025) Overexpression of the signaling coordinator GAB2 can play an important role in the progression of acute myeloid leukemia. J Clin Invest 135:e195929.
3. Sármay G et al. (2006) The multiple functions of the Grb2-associated binder (Gab) adaptor/scaffolding protein in immune cell signaling. Immunol Lett 104:76–82.
4. Zhang Y et al. (2023) Association of the GAB1 gene with asthma susceptibility and the efficacy of inhaled corticosteroids in children. BMC Pulm Med 23:493.