Disease relevance of Ras85D

• Noonan syndrome and related disorders: dysregulated RAS-mitogen activated protein kinase signal transduction [1].
• BACKGROUND: ERA (Escherichia coli Ras-like protein) is an E. coli GTP binding protein that is essential for proliferation [2].

High impact information on Ras85D

• We find that loss of tsc1 disrupts patterning due to a loss of temporal control of differentiation. tsc1 controls the timing of differentiation downstream or in parallel to the RAS/MAPK pathway [3].
• The Ras GTPase links extracellular mitogens to intracellular mechanisms that control cell proliferation [4].
• DOS, a novel pleckstrin homology domain-containing protein required for signal transduction between sevenless and Ras1 in Drosophila [5].
• Previous analyses have demonstrated that Ras1 (p21ras) operates upstream of the D-Raf (Raf1) serine/threonine kinase in this signaling pathway [6].
• By using a recently developed technique of germline mosaics, we find that D-Raf can be activated by torso in the complete absence of Ras1 [6].

Biological context of Ras85D

• Raf functions downstream of Ras1 in the Sevenless signal transduction pathway [7].
• The Ras GTPase links extracellular signals to intracellular mechanisms that control cell growth, the cell cycle, and cell identity [8].
• The Drosophila Ras1 gene is required for proper cell fate specification throughout development, and the loss-of-function phenotype of Ras1 suggests an additional role in cell proliferation or survival [9].
• A direct role for RAS1 in promoting cell proliferation, however, has not been established [9].
• Ectopic expression of activated Ras1 induces hyperplastic growth and increased cell death in Drosophila imaginal tissues [9].

Anatomical context of Ras85D

• Hedgehog and RAS pathways cooperate in the anterior-posterior specification and positioning of cardiac progenitor cells [10].
• These results suggest that Ras1 signaling during oogenesis involves novel components that may be intimately associated with additional signaling processes and with the reorganization of the cytoskeleton [11].
• We demonstrate that during embryogenesis Ras1 transcripts are restricted mainly to the embryonic central nervous system, suggesting that the gene product also may have a role in these nerve cells [12].
• One encodes the beta subunit of type I geranylgeranyl transferase, a prenylation enzyme essential for targeting RAS to the plasma membrane [13].
• Furthermore, we have analyzed the maternal-effect phenotype of Son of sevenless (Sos), a positive regulator of Ras1, and showed that embryos derived from germ cells lacking Sos+ activity exhibit a terminal-class phenotype [14].

Associations of Ras85D with chemical compounds

• PTP-ER, a novel tyrosine phosphatase, functions downstream of Ras1 to downregulate MAP kinase during Drosophila eye development [15].

Physical interactions of Ras85D

• An SH3-SH2-SH3 protein is required for p21Ras1 activation and binds to sevenless and Sos proteins in vitro [16].
• LRR47 belongs to a subfamily of LRR proteins that have in common the ability to interact with ras GTPase [17].

Regulatory relationships of Ras85D

• Transient misexpression of the activated Ras1 protein (Ras1V12) later in pupal development suppressed the Argos-induced cell death [18].
• Ectopic expression of PTP-ER dramatically inhibits RAS1/MAPK signaling [15].
• Both the lethality and the eye roughening caused by activated Dsrc were partially suppressed by mutations in the Drosophila Ras1 gene [19].
• Ras GTPase-activating proteins (GAPs) are negative regulators of ras, which controls proliferation and differentiation in many cells [20].

Other interactions of Ras85D

• Interactions between Ras1, dMyc, and dPI3K signaling in the developing Drosophila wing [8].
• Here, we show that the repressive effect of the RIR is counteracted by the ability of Src42 to associate, in an RTK-dependent manner, with a conserved region located immediately C-terminal to the RIR [21].
• To determine whether these Ras1 Enhancers function upstream or downstream of the Egf receptor, four mutations were tested for their ability to suppress an activated Egfr construct (lambdatop) expressed in oogenesis exclusively in the follicle cells [11].
• Ras1, the Drosophila homologue of p21, and the Rlb1 protein, are also non-cytoplasmic, membranous proteins [12].
• The expression of Rlc1 during embryogenesis is similar, but not identical, to the expression pattern detected for Ras1 [12].

Analytical, diagnostic and therapeutic context of Ras85D

• Sequence analysis of three dominant-negative alleles defines two regions of 14-3-3 epsilon that participate in RAS1 signaling [22].

References