The ras system in yeasts

The ras oncogenes are highly conserved in evolution. Homologs of these genes have been found in many eukaryotes, including unicellular 18, 23, 32, 75, 78 and complex multicellular organisms. 26, 40 70 It is likely that ras homologs will be found in all eukaryotic organisms. Certainly there are no other oncogenes presently known that are as highly conserved. The degree of identify between the mammalian oncogenic RAS proteins and the RAS proteins of the yeasts Saccharomyces cerevisiae (RASI and RAS2) and Schizosaccharomyces pombe (ras1) in the N terminal halves of the molecules is about 90%. To put this into perspective, the degree of identity between the cAMP-dependent protein kinase regulatory subunits from yeasts and mammals is in the range of 50%. 95 These subunits bind two molecules of cAMP apiece, dimerize, bind the catalytic sub-unit, release the catalytic subunit from inhibition upon binding cAMP, and retain the ability to interact with the catalytic subunit of the divergent organisms. 42, 111 From this example it is reasonable to infer that the level of conservation of primary structure observed for RAS is associated with the conservation of many biochemical functions. This inference is correct

Activation of the T24 Bladder-Carcinoma Transforming Gene Is Linked to a Single Amino-Acid Change

Several different transforming genes have been observed in the DNA of a variety of tumours and tumour cell lines of human and rodent origin by the ability of these genes to induce morphological transformation in NIH 3T3 cells1-5. The transforming gene found in a human bladder carcinoma cell line, T24, is H-ras-1, the human homologue of the Harvey sarcoma virus oncogene (v-H-ras)6-9. In the present study we have compared the H-ras-1 genes cloned from T24 and normal human DNA. The H-ras-1 gene cloned from T24 DNA induces transformation in NIH 3T3 cells, while the same gene cloned from normal cellular DNA does not. The functionally significant difference between the transforming and normal genes appears to be a single base mutation, which produces an amino acid change in the sequence of the proteins that the genes encode

Ras-associating domain proteins : a new class of cyclic nucleotide-gated channel modulators

The Ras is a protein subfamily of small GTPases that are involved in cellular signal transduction. Members of Ras family are all related in structure and regulate diverse cell behaviors. Ras-associating/binding (RA/RBD) domain-containing proteins perform several different functions ranging from tumor suppression to being oncoproteins. Their role in different biological processes may be unclear and highly divergent but what is clear is that they convergently function by interacting with Ras proteins through their RA/RBD subdomains directly or indirectly. Apart from interacting with Ras proteins, there is no perceptible relationship between these proteins or their highly unrelated protein bodies. The heterogeneity among these RA domains allows them to interact with Ras proteins of different types as well as several other proteins which contain similar motifs. Very recently, we have demonstrated that growth factor receptor bound protein 14 (Grb14) RA domain binds to photoreceptor cyclic nucleotide-gated channel (CNG) and inhibits its activity in vivo. In this study, we have examined two other RA domain-containing protein phosphates expressed in retina, PHLPP1, and PHLPP2 on CNG channel activity. Our data indicate that not all RA domain proteins are modulators of CNG channel, suggesting the existence of heterogeneity among several RA domain proteins.6 page(s