Rasputin, the Drosophila homologue of the RasGAP SH3 binding protein, functions in Ras- and Rho-mediated signaling

Abstract

The small GTPase Ras plays an important role in many cellular signaling processes. Ras activity is negatively regulated by GTPase activating proteins (GAPs). It has been proposed that RasGAP may also function as an effector of Ras activity. We have identified and characterized the Drosophila homologue of the RasGAP-binding protein G3BP encoded by rasputin (rin). rin mutants are viable and display defects in photoreceptor recruitment and ommatidial polarity in the eye. Mutations in rin/G3BP genetically interact with components of the Ras signaling pathway that function at the level of Ras and above, but not with Raf/MAPK pathway components. These interactions suggest that Rin is required as an effector in Ras signaling during eye development, supporting an effector role for RasGAP. The ommatidial polarity phenotypes of rin are similar to those of RhoA and the polarity genes, e.g. fz and dsh. Although rin/G3BP interacts genetically with RhoA, affecting both photoreceptor differentiation and polarity, it does not interact with the gain-of-function genotypes of fz and dsh. These data suggest that Rin is not a general component of polarity generation, but serves a function specific to Ras and RhoA signaling pathways.

Association ofrasGAPSH3 Binding Protein 1, G3BP1, andrasGAP120with Integrin Containing Complexes Induced by an Adhesion Blocking Antibody

“…The Drosophila homologue of G3BP, Rasputin (Rin), has been implicated in the generation of cell polarity. 50 Disruption of Rin leads to defects in photoreceptor recruitment and the establishment of ommatidial polarity. These mutants displays phenotypic similarities with animals expressing defects in Rho A.…”

Research Progress on the Structure and Function of G3BP

“…G3BP binds to the SH3 domain of the Ras-GTPase activating protein (GAP) in serum-stimulated cells, as first reported by Paker in 1996 (1). The homologue of G3BP in Drosophila is known as Rasputin, encoded by the Rin gene (2). G3BP-like proteins have also been identified in plants such as Arabidopsis thaliana (3).…”

PKR-dependent cytosolic cGAS foci are necessary for intracellular DNA sensing

“…An RNA/DNA and RNA/RNA helicase, G3BP1 has ATP-and magnesium-dependent activity that is not stimulated by replication protein A (18). G3BP1 also regulates several pathways including Ras signaling (16,19), c-Myc mRNA turnover (20,21), NF-B signaling (22) and human epidermal growth factor receptor 2 signaling (23), tumor progression, and metastasis (23)(24)(25)(26)(27). In addition, G3BP1 inhibits p53 expression by interacting with the deubiq-uitinase ubiquitin-specific peptidase 10, thus playing an important role in promoting oncogenesis (28).…”