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J Biol Chem, Vol. 274, Issue 25, 17837-17844, June 18, 1999

Identification of the stef Gene That Encodes a Novel Guanine Nucleotide Exchange Factor Specific for Rac1

Mikio HoshinoDagger §, Masaki SoneDagger , Masaki Fukataparallel **, Shinya Kurodaparallel Dagger Dagger , Kozo Kaibuchiparallel , Yo-ichi NabeshimaDagger §, and Chihiro HamaDagger §§

From the Dagger  Department of Molecular Genetics, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, the  Department of Pathology and Tumor Biology, Kyoto University Graduate School of Medicine, Yoshidakonoecho, Sakyo-ku, Kyoto 606-8501, the § Institute for Molecular and Cellular Biology, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, the parallel  Division of Signal Transduction, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma 630-0101, the ** Department of Biochemistry, Hiroshima University School of Medicine, Hiroshima 734-8551, the Dagger Dagger  Inheritance and Variation Group, Precursory Research for Embryonic Science and Technology, Japan Science and Technology Corporation, Kyoto 619-0237, and §§ Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, 4-1-8 Hon-cho, Kawaguchi, Saitama 332, Japan

The Rho family GTPases are involved in a variety of cellular events by changing the organization of actin cytoskeletal networks in response to extracellular signals. However, it is not clearly known how their activities are spatially and temporally regulated. Here we report the identification of a novel guanine nucleotide exchange factor for Rac1, STEF, which is related in overall amino acid sequence and modular structure to mouse Tiam1 and Drosophila 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 that from either RhoA or Cdc42. Expression of a truncated STEF protein in culture cells induced membrane ruffling with altered actin localization, which implies that this protein also activates Rac1 in vivo. The stef transcript was observed in restricted parts of mice, including cartilaginous tissues and the cortical plate of the central nervous system during embryogenesis. These findings suggested that STEF protein participates in the control of cellular events in several developing tissues, possibly changing the actin cytoskeletal network by activating Rac1.

Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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