ONLINE COVER This week's issue features a Research Article that defines a role for the catalytic activity of the Vav1 guanine nucleotide exchange factor (GEF) in T cell biology. The image shows a complex between the catalytic core of Vav1 in gray and its substrate, the Rac1 GTPase, in gold. The locations of Leu³³⁴ and Lys³³⁵ in the Dbl homology (DH) domain of Vav1 are indicated in red. These two amino acid residues make key contacts with Rac1 and are essential for the exchange reaction. Experiments with mice that have a knock-in mutation in these residues showed that Vav1 has both GEF-dependent and GEF-independent activities that are necessary for T cell development and activation. [Image: Steve Smerdon, MRC National Institute for Medical Research, London, UK]

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