GRB2: a pivotal protein in signal transduction

The growth factor receptor-bound protein-2 (GRB2) is essential for multiple cellular functions. Inhibition of GRB2 function impairs developmental processes in various organisms and blocks transformation and proliferation of various cell types. GRB2 is most well known for its ability to link the epidermal growth factor receptor tyrosine kinase to the activation of RAS and its downstream kinases, ERK1,2. We recently reported that GRB2 does not link the HER2 tyrosine kinase to the activation of ERK1,2 but to another kinase, AKT. So, different tyrosine kinases may converge on GRB2 for signaling; however, they may not always use GRB2 to effect the same downstream kinases for cellular functions. It is likely that GRB2 will be found to regulate many more kinases because it plays such a pivotal role in signal transduction.