Two actions of frabin: direct activation of Cdc42 and indirect activation of Rac
Open Access
- 20 June 2000
- journal article
- research article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 19 (27), 3050-3058
- https://doi.org/10.1038/sj.onc.1203631
Abstract
Frabin is an actin filament-binding protein which shows GDP/GTP exchange activity specific for Cdc42 small G protein and induces filopodium-like microspike formation and c-Jun N-terminal kinase (JNK) activation presumably through the activation of Cdc42. Frabin has one actin filament-binding (FAB) domain, one Dbl homology (DH) domain, first pleckstrin homology (PH) domain adjacent to the DH domain, one cysteine-rich FYVE domain, and second PH domain from the N-terminus to the C-terminus in this order. Different domains of frabin are involved in the microspike formation and the JNK activation, and the association of frabin with the actin cytoskeleton through the FAB domain is necessary for the microspike formation, but not for the JNK activation. We have found here that frabin induces the formation of not only filopodium-like microspikes but also lamellipodium-like structures in NIH3T3 and L fibroblasts. We have analysed the mechanism of frabin in these two actions and found that frabin induces filopodium-like microspike formation through the direct activation of Cdc42 and lamellipodium-like structure formation through the Cdc42-independent indirect activation of Rac small G protein. The FAB domain of frabin in addition to the DH domain and the first PH domain is necessary for the filopodium-like microspike formation, but not for the lamellipodium-like structure formation. The FYVE domain and the second PH domain in addition to the DH domain and the first PH domain are necessary for the lamellipodium-like structure formation. We show here these two actions of frabin in the regulation of cell morphology.Keywords
This publication has 20 references indexed in Scilit:
- Activation of G1 Progression, JNK Mitogen-activated Protein Kinase, and Actin Filament Assembly by the Exchange Factor FGD1Published by Elsevier BV ,1998
- Induction of filopodium formation by a WASP-related actin-depolymerizing protein N-WASPNature, 1998
- Involvement of Rho and Rac small G proteins and Rho GDI in Ca2+‐dependent exocytosis from PC12 cellsGenes to Cells, 1996
- Rho family GTPases: the cytoskeleton and beyondTrends in Biochemical Sciences, 1996
- The Dbl family of oncogenesCurrent Opinion in Cell Biology, 1996
- Rho as a regulator of the cytoskeletonTrends in Biochemical Sciences, 1995
- The Ras-Related Protein Cdc42Hs and Bradykinin Promote Formation of Peripheral Actin Microspikes and Filopodia in Swiss 3T3 FibroblastsMolecular and Cellular Biology, 1995
- Rho, Rac, and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodiaCell, 1995
- Isolation and characterization of the faciogenital dysplasia (Aarskog-Scott syndrome) gene: A putativeCell, 1994
- Identification of an invasion-inducing gene, Tiam-1, that encodes a protein with homology to GDP-GTP exchangers for Rho-like proteinsCell, 1994