Disease relevance of RICS

• Endogenous p200RhoGAP was localized to cortical actin in naive N1E-115 neuroblastoma cells and to the edges of extended neurites of differentiated N1E-115 cells [1].
• Suppression of GC-GAP expression by siRNA inhibited proliferation of C6 astroglioma cells [2].
• Exoenzyme T (ExoT) is a bifunctional type III cytotoxin of Pseudomonas aeruginosa that possesses both Rho GTPase-activating protein and ADP-ribosyltransferase activities [3].
• PURPOSE: The deleted in liver cancer-1 (DLC-1) gene that encodes a Rho GTPase-activating protein with tumor suppressor function is located on chromosome 8p21-22, a region frequently deleted in prostate carcinomas [4].
• Oligophrenin-1 is a recently discovered Rho-GTPase activating protein, mutation of which is associated with X-linked mental retardation [5].

High impact information on RICS

• Another pool of Grit was recruited to the activated receptor tyrosine kinase through its binding to N-Shc and CrkL/Crk, adapter molecules downstream of activated receptor tyrosine kinases [6].
• Overexpression of the TrkA-binding region of Grit inhibited NGF-induced neurite elongation [6].
• These results suggest that a Rho GTPase-activating protein may have a positive input to cell proliferation and provide evidence that p200 RhoGAP can mediate cross-talks between Ras- and Rho-regulated signaling pathways in cell growth regulation [7].
• p200 RhoGAP Promotes Cell Proliferation by Mediating Cross-talk between Ras and Rho Signaling Pathways [7].
• Here we show that ectopic expression of p200 RhoGAP stimulates fibroblast cell proliferation and cell cycle progression, leading to transformation [7].

Biological context of RICS

• Furthermore, the GTPase-activating protein activity of RICS was inhibited by phosphorylation by Ca(2+)/calmodulin-dependent protein kinase II [8].
• These results suggest that RICS is involved in the synaptic adhesion- and N-methyl-d-aspartate-mediated organization of cytoskeletal networks and signal transduction [8].
• Given that GC-GAP is specifically expressed in the nervous system and that it is localized to the dendritic processes of cultured neurons, GC-GAP may play a role in dendritic morphogenesis and also possibly in neural/glial cell proliferation [2].
• DLC1, a tumour suppressor gene inactivated in liver carcinogenesis and encoding a Rho GTPase activating protein (RhoGAP) maps to one of the deleted regions (8p21.3-22) [9].
• A putative Xenopus Rho-GTPase activating protein (XrGAP) gene is expressed in the notochord and brain during the early embryogenesis [10].

Anatomical context of RICS

• Thus, RICS may regulate dendritic spine morphology and strength by modulating Rho GTPases [8].
• Further, we found some tendency for neurite promotion in full-length Grit-overexpressing PC12 cells upon NGF stimulation [6].
• The p250GAP mRNA was enriched in brain, with high expression in cortex, corpus striatum, hippocampus, and thalamus [11].
• Expression of the RhoGAP domain of p200RhoGAP in Swiss 3T3 fibroblasts inhibited actin stress fiber formation stimulated by lysophosphatidic acid and platelet-derived growth factor-induced membrane ruffling but not Bradykinin-induced filopodia formation [1].
• Given that Fyn activity is up-regulated during oligodendrocyte maturation, the results argue that p250GAP is phosphorylated by Fyn in oligodendrocytes [12].

Associations of RICS with chemical compounds

• The mean recoveries of methenamine hippurate from spiked test plates for '180 Grit' Stainless Steel, Teflon and WARCO White (neoprene and PVC) gasket material were 77.2, 96.1 and 50.6%, with RSDs of +/- 9.4 (n = 25), +/- 4.3 (n = 25) and +/- 36% (n = 20), respectively [13].
• This 2S-method consists of: (1) Grit blasting on titanium surface in order to roughen it, and (2) thermo-chemical (TCh) treatment in order to obtain a bioactive surface with bone-bonding ability [14].

Regulatory relationships of RICS

• Tyrosine phosphorylation of p250GAP by Fyn would regulate its RhoGAP activity, subcellular localization, or interactions with other proteins, leading to morphological and phenotypic changes of oligodendrocytes [12].

Other interactions of RICS

• p250GAP, a neural RhoGAP protein, is associated with and phosphorylated by Fyn [12].

Analytical, diagnostic and therapeutic context of RICS

• Northern blot analysis revealed a brain-specific expression pattern of p200RhoGAP [1].
• Whole-mount in situ hybridization shows that maternal XrGAP transcripts are specifically expressed in the animal hemisphere of the eggs and blastula stage embryos [10].
• Northern blot and RT-PCR analysis show that a single XrGAP transcript is maternally expressed and gradually decreases afterwards [10].

References