Identification of the stef Gene That Encodes a Novel Guanine Nucleotide Exchange Factor Specific for Rac1*
- Mikio Hoshinoद,
- Masaki Sone‡,
- Masaki Fukata‖**,
- Shinya Kuroda‖‡,
- Kozo Kaibuchi‖,
- Yo-ichi Nabeshimaद and
- Chihiro Hamaत
- From the ‡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‖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 ‡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
Abstract
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 andDrosophila 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. Thestef 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.
Footnotes
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↵* This work was supported by CREST of Japan Science and Technology Corporation, by research grants from the Ministry of Education, Science, Sports, and Culture, and by a Research Grant for Nervous and Mental Disorders from the Ministry of Health and Welfare of Japan.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) .
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↵2 M. Sone and C. Hama, unpublished data.
- Abbreviations:
- GEF
-
guanine nucleotide exchange factor
- DH
-
Dbl homology
- PH
-
pleckstrin homology
- PCR
-
polymerase chain reaction
- RT
-
reverse transcription
- kb
-
kilobase pair(s)
- GTPγS
-
guanosine 5′-3-O-(thio)triphosphate
- GST
-
glutathione S-transferase
- PBS
-
phosphate-buffered saline
- HA
-
hemagglutinin
- En
-
embryonic day n
-
- Received November 11, 1998.
- Revision received March 3, 1999.
- The American Society for Biochemistry and Molecular Biology, Inc.
