Grb2, a simple adapter with complex roles in lymphocyte development, function, and signaling

Lymphocyte development, activation, and tolerance depend on antigen receptor signaling transduced via multiple intracellular signalosomes. These signalosomes are assembled by different adapters. Given that signaling molecules can be either positive or negative regulators for a biochemical target, the complex of a target with different regulator may dictate the final signaling outcome. Grb2 is a simple adapter known to be involved in a variety of growth factor receptor signaling. However, its role in antigen receptor signaling as well as lymphocyte development and function has emerged only recently. Despite its simple molecular structure, recent experiments show that Grb2 may play a complex role in T and B-cell antigen receptor signaling. In this article, we review recent findings about the physiological role of Grb2 in T and B-cell development and activation and summarize the current mechanistic understanding of how Grb2 exerts its function following T and B-cell antigen receptor stimulation.