Structural Conservation of Ras-Related Proteins and Its Functional Implications

  • P. Chardin
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 108 / 1)

Abstract

The H-ras, K-ras, and N-ras genes were discovered in the early 1980s (see Chap. 17). In 1983, soon after these first discoveries, an open reading frame located between the actin and tubulin genes of Saccharomyces cerevisiae was found to encode a protein sharing approximately 30% identity with mammalian ras proteins; it was named Ypt (see Chap. 27). One year later the rho genes were discovered, first in Aplysia, then in human. Rho proteins also shared approximately 30% identity with Ras or Ypt proteins (see Chap. 36). These discoveries of several proteins distantly related to Ras strongly suggested that Ras proteins belonged to a large family. Molecular genetic approaches were then undertaken to isolate new members of this family by homology probing. Two techniques have been highly successful in the discovery of new ras-related genes: the use of degenerate oligonucleotide mixes corresponding to conserved stretches of amino acids (usually the DTAGQE sequence around position 61) and low stringency hybridization with already isolated probes, sometimes from distant organisms. Another important strategy consisted in the biochemical isolation of small GTPases from various tissues on the basis of their GTP/GDP-binding ability and sequencing of short peptides to clone the corresponding cDNAs with oligonucleotide probes. Most of these proteins appeared closely related to the ones already discovered by molecular genetics. Several yeast mutants were also found to encode Ras-related proteins: SEC4, a secretion mutant (see Chap. 4), CDC42, a cell division cycle mutant (see Chap. 37), RSR1, a suppressor of CDC24, and SPI1, whose overexpression suppresses the “premature initiation of mitosis mutant”, pim1. Some ras-related genes from Dictyostelium, expressed at a specific time in development, have also been isolated, such as Ddras or sas1 and sas2. And a Caenorhabditis elegans mutant of vulval induction (let-60) was found to encode a Ras protein (Han and Sternberg 1990).

Keywords

Hydrolysis Magnesium Cysteine Serine Proline 

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© Springer-Verlag Berlin Heidelberg 1993

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  • P. Chardin

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