Gab1, a therapeutic target for allergic asthma?

The Grb-associated binder (Gab) family of proteins transduce cellular signals between receptors and intracellular downstream effectors, providing a platform for protein-protein interactions. Gab1, a key member of the Gab family (Gab1, Gab2, ad Gab3), has been shown to mediate cell signaling through tyrosine phosphatase SHP2 or phosphatidylinositol-3 (PI3K) kinase in response to a variety of the extracellular stimuli. The association of Gab1 with SHP2 and the p85 subunit of PI3K is essential for the activation of the Erk/MAPK, PI3K/Akt, and JAK/STAT pathways with diversified biological functions (1). Gab1 is also critical in other physiological activities. Conditional Gab1 knockout in mice showed impaired signal transduction with different system dysfunctions. For example, liver-specific Gab1 knockout mice showed defective liver regeneration (2), and cardiomyocyte-specific Gab1 knockout mice displayed an increase in infarct size and a decrease in cardiac function after ischemia/reperfusion injury (3).