Pierre Chardin

The ras superfamily proteins.

Several recent discoveries indicate that the ras genes, frequently activated to a transforming potential in some human tumours, belong to a large family that can be divided into three main branches: the first branch represented by the ras, ral and rap genes; the second branch, by the rho genes; and the third branch, by the rab genes. The C-terminal end of the encoded proteins always includes a cystein, which may become fatty-acylated, suggesting a sub-membrane localization. The ras superfamily proteins share four regions of high homology corresponding to the GTP binding site; however, even in these regions, significant differences are found, suggesting that the various proteins may possess slightly different biochemical properties. Recent reports show that some of these proteins play an essential role in the control of physical processes such as cell motility, membrane ruffling, endocytosis and exocytosis. Nevertheless, the characterization of the proteins directly interacting with the ras or ras-related gene-products will be required to precisely understand their function.

Identification of multiple ral gene products in human platelets that account for some but not all of the platelet Gn-proteins

Polyclonal antibodies raised against specific recombinant low molecular mass GTP‐binding proteins were tested for their ability to recognize partially purified human platelet membrane Gn‐proteins (i.e. proteins that bind [α‐32PlGTP on nitrocellulose blots of SDS/polyacrylamide gels). An antiserum against simian ralA protein recognized a 27 kDa human platelet protein with the same apparent molecular mass as the major platelet Gn‐protein (Gn27). In further analysis by two‐dimensional polyacrylamide gel electrophoresis, the isoelectric focusing step permitted resolution of 12 major Gn‐protein forms, seven of 27 kDa (Gn27a‐g), one of 26 kDa (Gn26) and four of 24 kDa (Gn24a‐d). The ralA antibody reacted strongly with the five most basic Gn27 species (a‐e), weakly with Gn26 and not at all with Gn27f, Gn27g or Gn24a‐d. We conclude that ral gene products account for some but probably not for all of the platelet Gn‐proteins.

The ras-related ral gene maps to chromosome 7p15-22

SummaryHuman cDNAs coding for the new protein ral that shares 50% homology with the ras proteins have been recently isolated. A 600-bp fragment carrying mainly the coding region was used to localize the ral gene by hybridization with sorted chromosomes and in situ hybridization. Direct molecular hybridization on sorted chromosomes using a single laser illumination allowed the assignment of the ral gene to a region of the flow karyotype containing chromosomes 7, 8 and X. With dual laser analysis ral was assigned to the fraction containing chromosome 7. In the 331 human metaphases hybridized with the 3H-labelled insert, the silver grain distribution showed a unique major signal on chromosome 7p15-22.

Structure of the Human ras Gene Family

To study the structure of the ras gene family, we devised an original oligonucleotide strategy and isolated cDNAs for several new ras-related proteins: the ra1A protein (50% a.a. identity with ras) and the rab proteins, related to the yeast YPT and SEC4 proteins. These new isolates, as well as drosophila D-ras3 and rho probes were then used to precise the structure of the ras family, in human.

STRUCTURE AND ORGANIZATION OF THE RAS GENE FAMILY, IN HUMAN

The H-ras, K-ras and N-ras genes code for 21kd GTP/GDP binding proteins possessing a weak GTPase activity and transiently anchored to the inner face of the plasma membrane by a palmitic acid covalently linked to their C-terminus.

Hypothesis: Brain size and skull shape as criteria for a new hominin family tree

Today, gorillas and chimpanzees live in tropical forests, where acid soils do not favor fossilization. It is thus widely believed that there are no fossils of chimpanzees or gorillas. However, four teeth of a 0.5-million-year (Ma)-old chimpanzee were discovered in the rift valley of Kenya (McBrearty and Jablonski, 2005), and a handful of teeth of a 10-Ma-old gorilla-like creature were found in Ethiopia (Suwa et al., 2007), close to the major sites of Homo discoveries. These discoveries indicate that chimpanzees and gorillas once shared their range with early Homo. However, the thousands of hominin fossils discovered in the past century have all been attributed to the Homo line. Thus far, our family tree looks like a bush with many dead-branches. If one admits the possibility that the australopithecines can also be the ancestors of African great apes, one can place Paranthropus on the side of gorilla ancestors and divide the remaining Australopithecus based on the brain size into the two main lines of humans and chimpanzees, thereby resulting in a coherent family tree.

The rap Proteins : GTP Binding Proteins Related to p21 ras with a Possible Reversion Effect on ras Transformed Cells

In .a wide variety of organisms, new ras-related genes have been identified on the basis of their sequence homologies with the mammalian H-ras, K-ras and N-ras proto-oncogenes. In mammals the proteins encoded by these ras-related genes have molecular weights of 21 000–24 000 daltons and share 30% to 50% homologies with the ras proteins (Chardin & Tavitian, 1986 ; Lowe et al. , 1987 ; Madaule & Axel, 1985 ; Touchot et al. , 1987) . By mutational analysis different regions of the ras proteins have been assigned to three functional domains: i) a carboxy-terminal region necessary for the anchorage of the protein to membranes, ii) an effector region (Willumsen et al., 1986; Sigal et al., 1986) that seems necessary for the interaction with the GTPase activating protein GAP (Trahey et al., 1987) and iii) a GTP binding domain (Barbacid, 1987). As ras transforming proteins detected in human tumors most frequently contain an amino acid substitution in the GTP binding domain, at either position 12, 13 or 61 (Barbacid, 1987) , this domain seems to play an essential role in the control of the biological properties of the protein.