The 'Gab' in signal transduction

Tyrosine phosphorylation plays an important role in controlling cellular growth, differentiation and function. Abnormal regulation of tyrosine phosphorylation can result in human diseases such as cancer. A major challenge of signal transduction research is to determine how the initial activation of protein-tyrosine kinases (PTKs) by extracellular stimuli triggers multiple downstream signaling cascades, which ultimately elicit diverse cellular responses. Recent studies reveal that members of the Gab/Dos subfamily of scaffolding adaptor proteins (hereafter, 'Gab proteins') play a crucial role in transmitting key signals that control cell growth, differentiation and function from multiple receptors. Here, we review the structure, mechanism of action and function of these interesting molecules in normal biology and disease.