Identification of the stef gene that encodes a novel guanine nucleotide exchange factor specific for Rac1

The Rho family GTPases are involved in a variety of cellular events by chan ging the organization of actin cytoskeletal networks in response to extrace llular signals. However, it is not clearly known how their activities are s patially and temporally regulated. Here we report the identification of a n ovel guanine nucleotide exchange factor for Rad, STEF, which is related in overall amino acid sequence and modular structure to mouse Tiam1 and Drosop hila SIF proteins. STEF protein contains two pleckstrin homology domains, a PDZ domain and a Dbl homology domain. The in vitro assay showed that STEF protein specifically enhanced the dissociation of GDP from Rac1 but not tha t from either RhoA or Cdc42. Expression of a truncated STEF protein in cult ure cells induced membrane ruffling with altered actin localization, which implies that this protein also activates Rad in vivo. The stef transcript w as observed in restricted parts of mice, including cartilaginous tissues an d the cortical plate of the central nervous system during embryogenesis. Th ese findings suggested that STEF protein participates in the control of cel lular events in several developing tissues, possibly changing the actin cyt oskeletal network by activating Rad.