Disease relevance of ras

• Over-expression of this cDNA in Escherichia coli yielded a product of the predicted size, which was demonstrated to possess IMPD activity in a spectrophotometric assay [1].
• We cloned a Drosophila melanogaster ras gene (Dmras64B) on the basis of its homology to the ras oncogen from Harvey murine sarcoma virus [2].
• The name ras was assigned to this gene family based on the species of origin of the viral oncogenes of the rat-derived Harvey and Kirsten murine sarcoma viruses [3].

High impact information on ras

• These studies provide further insights into the function of ras as an oncogene [4].
• These results demonstrate a requirement of Jun downstream of the sevenless/ras signaling pathway for neuronal development in the Drosophila eye [5].
• Drosophila Rap1 protein is 88% identical to human rap1A/K-rev1 protein, a putative antagonist of ras action [6].
• The other locus encodes a protein that is homologous to the S. cerevisiae CDC25 protein, an activator of guanine nucleotide exchange by ras proteins [7].
• The Drosophila ras oncogenes: structure and nucleotide sequence [8].

Biological context of ras

• The change of expression of an MR-induced mutation to a weaker phenotype or to the wild-type occurred at a frequency of 3.3 X 10(-3) (ras) to 20.4 X 10(-3) (sn) [9].
• Investigation of an enhancer-trap line exhibiting testis-specific beta-galactosidase expression led to the isolation of the Drosophila gene encoding inosine monophosphate dehydrogenase (IMPD), the rate-limiting enzyme in guanine nucleotide synthesis, which has been implicated in cell cycle control and malignant transformation [1].
• A transcribed DNA segment adjacent to the P insert encodes an amino acid sequence that is similar to known inosine monophosphate dehydrogenase (IMPDH) sequences [10].
• Translation of the impdh cDNA nucleotide sequence indicated that the Drosophila IMPDH exhibited 48% and 65% amino acid identity to the Leishmania donovani and human isoform II counterparts, respectively [11].
• In situ hybridization of the cloned impdh cDNA probe to Drosophila salivary gland chromosomes indicated that the impdh gene is located at position 9E1-4 on the X chromosome [11].

Anatomical context of ras

• Prior experiments have detected proteins coded for by ras genes in a large number of normal cells, cell lines, and tumors [3].
• In larvae, ras transcripts are restricted to dividing cells (e.g., imaginal disks, gonads, and brain) [12].
• It is also expressed in specialized tissues in which intensive exocytic/endocytic cycles take place, including the garland cells, a small group of nephrocytes which take up waste materials from the hemolymph by endocytosis. rop is regulated by a bidirectional promoter shared with Ras2, a member of the R-ras/TC21 branch of the ras supergene family [13].

Associations of ras with chemical compounds

• The induction of visible mutations by MR is observed at only a limited number of genes, such as singed bristle (sn), raspberry eye colour (ras), yellow body colour (y) and a carmine eye colour (car) [9].
• Identification of IMPDH as a probable product of the ras gene is compatible with the finding of an allele that requires dietary guanosine (GR), since the enzyme mediates the first of two biosynthetic steps leading from inosine monophosphate (IMP) to guanosine monophosphate (GMP) [10].
• As in the Drosophila Dras3 protein, both rap proteins have a threonine instead of the glutamine found at position 61 of the classical ras proteins [14].
• Of 24 ethyl methanesulphonate-induced, recessive-lethal mutations in the region 9E1-9F13 of the X chromosome of Drosophila melanogaster, eight fall into a typically homogeneous lethal complementation group associated with the raspberry (ras) locus [15].

Physical interactions of ras

• These results establish that, in the absence of calcium, both squid and Drosophila CE bind GTP at near-physiological concentrations and hydrolyze GTP at rates comparable to unactivated ras [16].

Regulatory relationships of ras

• Ras GTPase-activating proteins (GAPs) are negative regulators of ras, which controls proliferation and differentiation in many cells [17].

Other interactions of ras

• We show that aveugle is required between ras and raf for EGFR signaling in the eye and for mitogen-activated protein kinase phosphorylation in cell culture. aveugle encodes a small protein with a sterile alpha motif (SAM) domain that can physically interact with the scaffold protein connector enhancer of Ksr (Cnk) [18].
• We describe the developmental effects of the expression of a normal and mutated Drosophila ras gene ras2 in transgenic Drosophila [19].
• At the amino acid level, the sequence shows 68% identity and 81% similarity to bovine smg p25a GDP dissociation inhibitor (GDI), a regulator of ras-like small GTPases of the rab/SEC4/YPT1 subfamily [20].
• The guanine nucleotide exchange factor CNrasGEF activates ras in response to cAMP and cGMP [21].
• However, a decrease in ras signaling results in enhancement of the phenotype caused by the ro-svp transgene [22].

Analytical, diagnostic and therapeutic context of ras

• Cloning and sequence analysis of a Drosophila melanogaster cDNA encoding IMP dehydrogenase [11].
• A Gly14----Val14 mutant (Gly14 in ras2 is equivalent to Gly12 in mammalian ras proteins) was constructed in ras2 by site-directed mutagenesis [19].

References