Disease relevance of Rap1a

• Toward understanding the mechanism of action of Krev-1 protein, we constructed a series of point mutants of Krev-1 cDNA and tested their biological activities in DT cells and HT1080 human fibrosarcoma cells harboring the activated N-ras gene [1].
• A 1.8 kb cDNA clone, Krev-1, with revertant-inducing activity on Kirsten sarcoma virus-transformed NIH/3T3 cells, has been isolated from a human fibroblast cDNA expression library [2].
• Partial suppression of tumorigenicity in a human lung cancer cell line transfected with Krev-1 [3].
• A human non-small-cell lung carcinoma cell line, Calu-6 (from an anaplastic carcinoma), was transfected with the Ki-ras-related anti-oncogene Krev-1 [3].

High impact information on Rap1a

• In Krev-1 transfectants, there is a correlation between the levels of specific mRNA and the degrees of suppression of the transformed phenotype [2].
• Kirsten-ras-revertant 1 (Krev-1) cDNA encodes a ras-related protein and exhibits an activity of inducing flat revertants at certain frequencies (2-5% of total transfectants) when introduced into a v-K-ras-transformed mouse NIH 3T3 cell line, DT [1].
• These findings are consistent with the idea that Krev-1 protein is regulated like many other G proteins by the guanine triphosphate/guanine diphosphate-exchange mechanism probably in response to certain negative growth-regulatory signals [1].
• Microinjection of smg/rap1/Krev-1 p21 into Swiss 3T3 cells induces DNA synthesis and morphological changes [4].
• The Krev-1 gene has been shown to suppress ras-mediated transformation in vitro [5].

Associations of Rap1a with chemical compounds

• Neutrophils from Rap1a-/- mice had reduced fMLP-stimulated superoxide production as well as a weaker initial response to phorbol ester [6].
• The phospholipase C inhibitor U-73122 abolished carbachol- but not forskolin-induced Rap1 activation [7].

Biological context of Rap1a

• Rap1a-rs1, which was not localized, has a sequence very similar to the Rap1a cDNA, suggesting that it has been recently acquired by the mouse genome [8].
• smg/rap1/Krev-1 p21s inhibit the signal pathway to the c-fos promoter/enhancer from c-Ki-ras p21 but not from c-raf-1 kinase in NIH3T3 cells [9].

Anatomical context of Rap1a

• Association of Rap1a and Rap1b proteins with late endocytic/phagocytic compartments and Rap2a with the Golgi complex [10].

Regulatory relationships of Rap1a

• smg/rap1A/Krev-1 p21 cDNA is known to inhibit v-Ki-ras p21-induced cell transformation in NIH3T3 cells, but the inhibitory mechanism is not clear at present [9].

Other interactions of Rap1a

• In this study, five amino acid residues flanking the ras effector domain, which are not conserved with the Krev-1 protein, were shown to be required for normal protein-protein interactions and biological activity [5].
• The levels of PEA3 and PEG-3 RNA and proteins are elevated in the oncogenically transformed CREF cells, and reduced in transformation and tumorigenic suppressed Ha-ras/Krev-1 doubly transformed CREF cells [11].

References