Characterization of RAC3, a Novel Member of the Rho Family*
- From the Section of Molecular Carcinogenesis, Department of Pathology, Children’s Hospital Los Angeles Research Institute and School of Medicine, University of Southern California, Los Angeles, California 90027
Abstract
The small GTP-binding proteins Rac1 and Rac2 are critically important in regulating multiple signal transduction pathways in eukaryotic cells. Here we report the isolation of a novel third Rac family member, Rac3. Rac3 differs from Rac1/2 at its carboxyl-terminal end, a domain associated with subcellular localization and binding to specific cellular regulators.RAC3 mRNA expression patterns differ from those ofRAC2, which is hematopoietic specific and also from those of RAC1. The RAC3 gene was mapped to chromosome 17q23–25, a region frequently deleted in breast cancer. Rac3 protein levels are not affected by organization of the actin cytoskeleton but remarkably, are serum-inducible. Rac3 is an active GTPase, and this activity is regulated by Bcr. When constitutively activated, Rac3 is able to stimulate efficiently the c-Jun amino-terminal kinase signaling pathway. These findings support a role for Rac3 in intracellular signaling.
Footnotes
-
↵* This work was supported in part by funds provided by the Breast Cancer Fund of the State of California through the Breast Cancer Research Program of the University of California Grant 1RB-0001 and by Public Health Service National Institutes of Health Grants CA47456 and CA 50248.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) .
-
↵‡ To whom correspondence should be addressed: Section of Molecular Carcinogenesis, Department of Pathology, Ms 103, Childrens Hospital Los Angeles Research Institute, 4650 Sunset Blvd., Los Angeles, CA 90027.
-
↵1 The abbreviations used are: JNK, c-Jun amino-terminal kinase; kb, kilobase(s); GST, glutathioneS-transferase.
-
↵2 L. Haataja, J. Groffen, and N. Heisterkamp, unpublished observations.
-
- Received May 2, 1997.
- Revision received June 10, 1997.
